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Interferon-induced protein 44-like (IFI44L) gene is a type I interferon-stimulated gene (ISG) that plays a critical role in antiviral activity and constitutes a promising diagnostic marker. However, its precise role and function in tuberculosis have not been unveiled. This study showed that IFI44L acts as an antimicrobial target and positive modulator in human macrophages. Knockdown of IFI44L led to increased Mycobacterium tuberculosis intracellular survival. Moreover, IFI44L was significantly upregulated, and it restricted the intracellular survival of M. tuberculosis H37Rv strains at 72 h after rifampicin treatment. Individuals with cutaneous tuberculosis (CTB) were found to have significantly higher IFI44L expression after 6 months of rifampicin therapy than after only 1 month. These results demonstrated that IFI44L induced positive regulation and clearance of M. tuberculosis from human macrophages. This antimicrobial activity of IFI44L makes it a possible target for therapeutic applications against M. tuberculosis ., Competing Interests: The authors have no conflicts of interest to declare., (Copyright © 2021 Haiqin Jiang et al.)

Cutaneous tuberculosis is a rare extrapulmonary manifestation of tuberculosis which, like disseminated tuberculosis, commonly occurs in immunocompromised patients. Poncet reactive arthritis is a seronegative arthritis affecting patients with extrapulmonary tuberculosis, which is uncommon even in endemic countries. We report a previously healthy 23-year-old male patient with watery diarrhea associated with erythematous ulcers on the lower limbs and oligoarthritis of the hands. Histopathological examination of the skin showed epithelioid granulomatous process with palisade granulomas and central caseous necrosis. AFB screening by Ziehl-Neelsen staining showed intact bacilli, the culture was positive for Mycobacterium tuberculosis, and colonoscopy revealed multiple shallow ulcers. Disseminated tuberculosis associated with reactive Poncet arthritis was diagnosed, with an improvement of the clinical and skin condition after appropriate treatment., (Copyright © 2020 Sociedade Brasileira de Dermatologia. Published by Elsevier España, S.L.U. All rights reserved.)

Cutaneous tuberculosis (CTB) is a challenging diagnosis that often requires tissue biopsy and the use of immunohistochemical (IHC) staining, among other special stains. The mycobacterium tuberculosis IHC stain is believed to be specific for mycobacteria and closely related organisms, without documented reactivity to normal human tissue. In this study, we document 4 cases of previously unreported cross-reactivity between the mycobacterium tuberculosis IHC polyclonal antibody and normal eosinophil granules in patients without other evidence of CTB infection. Such cross-reactivity represents a potential pitfall for the use of IHC in the diagnosis of CTB.

Cutaneous lesions in the presence of fever in patients undergoing immunosuppressive therapy are a diagnostic challenge and may represent manifestations of multiple diseases, such as fungal infections, nocardiosis, lymphoproliferative diseases, zoonosis, and tuberculosis. The authors report a case of a 66-year-old white man with chronic kidney disease since 2014 (chronic pyelonephritis) who had a renal transplant in the previous 6 months. Induction therapy was performed with thymoglobulin, and his current immunosuppression scheme included tacrolimus, mycophenolate mofetil, and prednisolone. The patient had no history of pulmonary tuberculosis. The patient presented with 2 cutaneous lesions, localized on the back and abdomen, that appeared to be firm, painful, subcutaneous, erythematous nodules with an approximately 5 cm diameter overlying an infected focus and purulent material inside. The patient also had a fever and fatigue. Blood analysis showed pancytopenia with an elevation of inflammatory markers and graft dysfunction. Tissue cultures and skin biopsy with histological analysis were performed. Histopathology of the lesion showed a nonspecific inflammatory infiltrate without granulomas, and acid-fast bacillus staining was negative. Nevertheless, serum QuantiFERON testing was positive. But polymerase chain reaction finally confirmed the presence of Mycobacterium tuberculosis, which confirmed the diagnosis of cutaneous tuberculosis. A chest computed tomography scan showed a lung pattern of miliary tuberculosis. The patient was treated with multidrug tuberculosis therapy, resulting in lesion clearance after 3 weeks. Tuberculosis is a serious infection, especially in high-risk patients, such as those in an immunocompromised state. The incidence of cutaneous tuberculosis is rare, but it should be considered in patients presenting with atypical skin lesions suggestive of an underlying infectious etiology., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Tuberculous gummas are an unusual form of tuberculosis (TB) accounting for 1%-2% of all cutaneous TB cases. The aim of this article was to describe the epidemiological, clinical, bacteriological, immunological, and therapeutic features of this form upon a case report and a literature review. Forty-eight case reports were identified through a PubMed and Google Scholar search using the following keywords: "tuberculous gumma" and "metastatic tuberculous abscesse." Tuberculous gumma can occur at any age. Immunodepression is not a sine qua non condition to the development of the disease. Limbs are the most frequent site for gummas. Tuberculous gummas are associated to another location in only 73% of cases. The most frequent associated locations are lung, nodes, and musculoskeletal apparatus. Mantoux test is negative in 38% of cases. Skin stain is positive in 45% of cases and culture in 85% of cases. Giant epithelioid cell granuloma is present in 82.4% of cases. There is no universally accepted chemotherapy regimen for metastatic tuberculous abscesses. The classic 2RHZE/4RH is highly effective., Competing Interests: There are no conflicts of interest

Dr. Tomisaku Kawasaki was the first to describe BCG reactivation in Kawasaki Disease (K D ), and this sign is present in about 30-50% of K D patients. It is a very specific early sign of the disease and although it has been recognized for decades, its pathophysiology continues to be an enigma. Recently, Yamada et al. reported a severe BCG reaction with tuberculid in 2 Japanese K D patients. We present 2 cases with K D and severe BCG reaction, one from Japan and the other from Mexico and review the policies of administration of BCG in both countries. The BCG vaccine has a worldwide coverage of 88%. Differences in BCG strains and methods of administration may influence BCG reactions in K D . The BCG reaction in the inoculation site may represent the most useful sign in K D .

Tuberculosis is a chronic infectious disease, which caused by Mycobacterium tuberculosis. It typically affects the functions of the lung and causes high morbidity and mortality rates worldwide. The lectin pathway, one of the complement cascade systems, provides the primary line of defense against invading pathogens. However, what is the specific effection between tuberculosis and complement is unknown. Mannose-binding lectin (MBL), a recognition subunit, binds to arrays of carbohydrates on the surfaces of pathogens, which results in the activation of MBL-associated serine protease-2 to trigger a downstream reaction cascade of complement system. The effects of human MBL-associated serine protease-2 (hMASP-2) were assessed in a rabbit-skin model by intradermal injection of 5 × 10 6 viable BCG bacilli. The rAd-hMASP-2 accelerated the formation of liquefaction and healing of the granuloma lesions, reduced the bacteria loads of the skin nodules. The serum levels of IL-2 and IFN-γ were significantly increasing during the granuloma and liquefaction phases in the rAd-hMASP-2 group. This study suggests that hMASP-2 can induce a protective efficacy in BCG-infected rabbit skin models, which affects both the progress of lesions and the survival of the mycobacteria within them., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Tuberculosis Verrucosa Cutis (TBVC), a verrucous form of cutaneous tuberculosis, occurs from inoculation of tubercle bacilli into the skin of a previously sensitized patient with moderate to high degree of immunity. This disease is now rare in western countries and in India; the incidence of cutaneous tuberculosis has fallen from 2% to 0.15%. However two recent studies from the Indian subcontinent have reported the prevalence of cutaneous tuebrculosis as 0.7% (Varshney et al) and 0.26% (Patra et al) This case is reported to demonstrate the indolent and extensive nature of tuberculosis verrucosa cutis in an immunocompetent individual and to highlight the importance of histopathology and empirical antitubercular therapy as an adjunct diagnostic tool.

Tuberculous chancre is an extremely rare form of cutaneous tuberculosis. The genital area is a possible site of presentation. We present a case of a young male with a persistent balanopreputial ulceration resembling a luetic chancre with negative serology for syphilis. The diagnosis was based on the specific pathologic features and the positive intradermal reaction to tuberculin. A successful treatment was achieved by combining antituberculosis treatment and surgical approach with circumcision. After six months of antituberculosis treatment, the patient developed paradoxical inguinal lymph node enlargement, which, after surgical excision and biopsy, was not followed by a relapse of the disease and needed no further therapy. Tuberculosis should be considered a potential diagnosis in the case of a persistent genital ulcer.

The genus Mycobacterium comprises more than 150 species, including important pathogens for humans which cause major public health problems. The vast majority of efforts to understand the genus have been addressed in studies with Mycobacterium tuberculosis. The biological differentiation between M. tuberculosis and nontuberculous mycobacteria (NTM) is important because there are distinctions in the sources of infection, treatments, and the course of disease. Likewise, the importance of studying NTM is not only due to its clinical significance but also due to the mechanisms by which some species are pathogenic while others are not. Mycobacterium avium complex (MAC) is the most important group of NTM opportunistic pathogens, since it is the second largest medical complex in the genus after the M. tuberculosis complex. Here, we evaluated the virulence and immune response of M. avium subsp. avium and Mycobacterium colombiense, using experimental models of progressive pulmonary tuberculosis and subcutaneous infection in BALB/c mice. Mice infected intratracheally with a high dose of MAC strains showed high expression of tumor necrosis factor alpha (TNF-α) and inducible nitric oxide synthase with rapid bacillus elimination and numerous granulomas, but without lung consolidation during late infection in coexistence with high expression of anti-inflammatory cytokines. In contrast, subcutaneous infection showed high production of the proinflammatory cytokines TNF-α and gamma interferon with relatively low production of anti-inflammatory cytokines such as interleukin-10 (IL-10) or IL-4, which efficiently eliminate the bacilli but maintain extensive inflammation and fibrosis. Thus, MAC infection evokes different immune and inflammatory responses depending on the MAC species and affected tissue.

Background: Mycobacterium tuberculosis (MTB) infection has been suggested to contribute to the pathogenesis of erythema nodosum (EN) and nodular vasculitis (NV), the classic forms of panniculitis. However, there is little evidence to demonstrate the presence of MTB in the skin lesions. This study is aimed at evaluating the association between MTB infection and the development of EN and NV in a Chinese population., Methods: A total of 107 patients (36 EN, 27 NV, and 44 others) with vasculitis and 40 control cases with other skin diseases were recruited and their skin lesion samples were subjected to real time polymerase chain reaction (PCR) analysis of the IS6110 and mpt64 gene fragments of MTB. Their blood mononuclear cells were tested for MTB antigen-specific IFN-γ responses by QuantiFERON®-TB Gold In-Tube (IT) assays., Results: PCR analysis revealed that 7/23 (30.4%) and 7/18 (38.9%) of the EN and NV samples were positive for the IS6110 DNA, respectively, which were significantly higher than 3/34 (8.8%) of other vasculitis (OV) and 3/40 (7.5%) of the control samples (p<0.05). The nested Real-Time PCR assay indicated that 6/7 (86%) of the IS6110-positive EN samples, all of the IS6110-positive NV and control samples, but only 1/3 of the IS6110-positive OV samples, were positive for the mpt64 gene. Similarly, 19/32 (59.4%) of the EN patients, 20/26 (76.9%) of the NV patients, and 17/36 (47.2%) of the OV patients were positive for MTB antigen-specific IFN-γ responses, which were significantly higher than 6/40 (15%) of the controls (p<0.05)., Conclusion: Our data strongly suggest that MTB infection and active TB are associated with the development of NV and EN in Chinese.

Disseminated bacillus Calmette-Guérin infection (BCGitis) is an uncommon condition which is usually associated with primary immunodeficiency. Skin histopathology findings have been described in rare cases only. A retrospective clinicopathological study was performed to assess the potential utility of skin biopsies in the diagnosis, prognosis and follow-up of these patients. Four cases of disseminated BCGitis in children with Severe Combined ImmunoDeficiency were biopsied before and after Haematopoietic Stem Cell Transplantation (HSCT). The results were compared to the clinical and immunological status of the children. Early skin biopsies revealed either dense dermal infiltration by foamy macrophages filled with acid fast bacilli (AFB) or mycobacterial spindle-cell pseudotumors rich in AFB. There were no granulomas. These patterns led to the diagnosis of disseminated BCGitis potentially caused by severe immunodeficiency. After HSCT, repeated skin biopsies were performed on persistent or new cutaneous lesions to rule out immune reconstitution inflammatory syndrome and to check for tuberculoid granulomas. One patient died of BCGitis combined with graft versus host disease. The 3 others presented with progressive-onset well differentiated granulomas over a long period and recovered. Skin biopsy is a useful part of the diagnostic workup for disseminated BCGitis, directing the clinician toward severe immunodeficiency. Moreover, skin biopsy may be a useful means of monitoring immune restoration for prognostic purposes., (Copyright © 2012 John Wiley & Sons A/S.)

Background: Tuberculosis (TB) is a serious infection afflicting a multitude of people worldwide. Recently, its prevalence has increased. The incidence of skin involvement generally is low. Bacillus Calmette-Guérin (BCG) is a live attenuated strain of Mycobacterium bovis that typically is administered as a vaccine to stimulate the immune system when treating some early neoplasms or to guard against tuberculosis., Methods: Case report and literature review., Case Report: The authors describe a young man with osteosarcoma of the left hemipelvis who received intradermal BCG injection for immune stimulation prior to surgery. In the course of neoadjuvant chemotherapy, he developed cutaneous tuberculosis., Conclusion: It is our opinion that BCG injection should be avoided in all patients requiring surgery, especially in oncologic patients, where the immunodeficiency brought on by chemotherapy predisposes to active opportunistic infection.

Interferon-γ receptor-1 (IFNγR1) deficiency is caused by mutations in the IFNγR1 gene and is characterized mainly by susceptibility to mycobacterial disease. Herein, we report an 8-month-old boy with complete recessive IFNγR1 deficiency, afflicted by recurrent mycobacterial diseases with Mycobacterium bovis, Mycobacterium tuberculosis, Mycobacterium avium intracellulare and Mycobacterium fortuitum. Genetic analysis showed a homozygous mutation (106insT) in the IFNγR1 gene leading to complete IFNγR1 deficiency. In addition, he had atypical mycobacterial skin lesions caused by M. avium intracellulare and developed scrotal and lower limb lymphedema secondary to compression of large and fixed inguinal lymphadenopathies. Hematopoietic stem cell transplantation was performed from a matched unrelated donor at 5 years of age; however, he died at 9 months post-transplant. To our knowledge, the patient is the first case with IL-12/IFN-γ pathway defect and severe lymphedema. We have also reviewed and summarized the literature related with IFNγR1 deficiency.

Bacterial cultures are the gold standard for diagnosing cutaneous tuberculosis, but there are limitations, despite the advances embracing the innovative technologies, including interferon yrelease assays, enzyme-linked immunoabsorbant assay, and molecular diagnostics, in addition to conventional skin tests and microscopic pathology. The results and their interpretation of cultures are reviewed for use in day-to-day practice.

The presence of γδ T cell receptor (TCR)-expressing cells in the epidermis of mice, termed dendritic epidermal T cells (DETCs), is well established. Because of their strict epidermal localization, it is likely that DETCs primarily respond to epithelial stress, such as infections or the presence of transformed cells, whereas they may not participate directly in dermal immune responses. In this study, we describe a prominent population of resident dermal γδ T cells, which differ from DETCs in TCR usage, phenotype, and migratory behavior. Dermal γδ T cells are radioresistant, cycle in situ, and are partially depend on interleukin (IL)-7, but not IL-15, for their development and survival. During mycobacterial infection, dermal γδ T cells are the predominant dermal cells that produce IL-17. Absence of dermal γδ T cells is associated with decreased expansion in skin draining lymph nodes of CD4(+) T cells specific for an immunodominant Mycobacterium tuberculosis epitope. Decreased CD4(+) T cell expansion is related to a reduction in neutrophil recruitment to the skin and decreased BCG shuttling to draining lymph nodes. Thus, dermal γδ T cells are an important part of the resident cutaneous immunosurveillance program. Our data demonstrate functional specialization of T cells in distinct microcompartments of the skin.

There are no pathognomonic findings for cutaneous infection caused by Mycobacterium chelonae. The type and duration of therapy varies considerably among reports and no single antibiotic is considered the treatment of choice. A 61-year-old patient, suffering from rheumatoid arthritis (treated with metotrexate and salazopyrine), presented with violaceous nodules of the right leg that had been evolving for 6 months. She was underwent several skin biopsies. Tissue culture of the last showed an atypical mycobacteria, identified as M. chelonae. Despite improvement after a two-week course of treatment with clarithromycin, a switch to ciprofloxacin was made because of gastrointestinal intolerance. After 3 months, only slight improvement of the lesions was achieved and clarithromycin was reintroduced; significant clinical improvement occurred by the third month. Clarithromycin was continued a further two months until the patient quit on her own and. no recurrence was observed. Infections caused by M. chelonae frequently occur in the setting of immunological impairment. Contaminated water is the natural reservoir, but we were unable to establish the source of contamination. As was previously described, there was a significant delay between clinical presentation and diagnosis. Thus, a high index of suspicion and multiple biopsies with culture are of paramount importance to confirming the diagnosis.

Buruli ulcer disease (BUD) is an emerging human disease caused by infection with Mycobacterium ulcerans, which leads to the development of necrotic skin lesions. The pathogenesis of the ulcer is closely associated with the production of mycolactone, a diffusible cytotoxin with immunomodulatory properties. To identify immunological correlates of BUD, we performed a broad screen of inflammatory mediators in serum samples and stimulated whole-blood supernatants of patients. We found that patients with active ulcers displayed a distinctive profile of immune suppression, marked by the down-modulation of selected chemokines and an impaired capacity to produce Th1, Th2, and Th17 cytokines on stimulation with mitogenic agents. These immunological defects were induced early in the disease and resolved after anti-BUD therapy, establishing their association with the presence of M. ulcerans. Interestingly, some of the defects in cytokine and chemokine response could be mimicked in vitro by incubation of CD4(+) peripheral blood lymphocytes with mycolactone. Our findings support the hypothesis that mycolactone contributes to bacterial persistence in human hosts by limiting the generation of adaptive cellular responses. Moreover, we identified immunological markers of BUD, which may be helpful for confirmatory diagnosis of the disease and, especially, for monitoring the response to antibiotic treatment.

Cutaneous tuberculosis (TB) is an extrapulmonary form of tuberculosis, which may be classified based on the immunologic state of the host. Chemotherapy still remains the treatment of choice. The management of cutaneous TB follows the same guidelines as that of TB of other organs, which can be treated with a short course four-agent chemotherapeutic regimen given for 2 months followed by a two-drug regimen for the next 4 months. This chapter highlights current treatment recommendations for cutaneous TB. The important factors to consider in the choice of optimal treatment includes the type of cutaneous involvement, stage of the disease, level of immunity, and general condition of the patient. The highest priority in any cutaneous TB control program is the proper, accurate, and rapid detection of cases and the availability of chemotherapy to all tuberculosis patients until cure. Contact tracing is also an important component of efficient tuberculosis control.

Background: Dermatologic conditions are often an early clue to human immunodeficiency virus (HIV) infection. As the disease progresses and the host immunity fails, patients may develop a number of skin conditions. At this point, they have a dominant T helper 2 immunologic response. After the initiation of antiretroviral therapy, the T helper 1 response is restored, and some skin problems, paradoxically, make their appearance then., Conclusion: Herpes zoster, mucocutaneous herpes, eosinophilic folliculitis, and mycobacterial infections have been known to occur at this stage. This may be because immune restoration of a host's immunity causes recognition of silent or latent infection and results in development of the condition. We report five cases that were seen at our center during a 2-year period.

We present a 33-year-old HIV-positive man who presented with a two-year history of a non-itchy papular eruption, associated with night sweats, headaches, poor memory and weight loss. On examination, he had erythematous papular lesions with necrotic centres on the face, arms and torso with no systemic abnormalities. A skin biopsy eventually led to the diagnosis of papulonecrotic tuberculid, and treatment with quadruple therapy resulted in resolution of his rash and systemic symptoms. Papulonecrotic tuberculid is thought to be a immunological response to Mycobacterium bacillus components in a previously sensitized patient following haematogenous spread from a focus of infection elsewhere. Cultures from the skin are typically negative and there are no acid-fast bacilli seen, but mycobacterial DNA can be detected using polymerase chain reaction. This case is an example of the paradoxical activation of the immune system seen in patients with HIV. It highlights the importance of skin biopsy in patients with unexplained systemic symptoms and a rash, as the differential diagnosis can be wide in HIV.

The decreased incidence of infectious diseases in developed countries may make their diagnosis difficult. Cutaneous tuberculosis is an example of this fact. A 44-year-old man presented with two painful abscesses on his lower extremities, which developed into chronic ulcers. A cutaneous biopsy revealed necrotizing granulomas in the dermis. Ziehl-Neelsen and periodic acid-Schiff stain were negative. Mantoux test was positive. Tc-99m scintigraphy showed increased uptake in the bone tissue of the left ankle and right tibiae, without direct relation to cutaneous lesions. Chest X-ray showed micronodular, apical, bilateral infiltrates, reduced volume of the right lung, and cavitation of the right superior lobe. Mycobacterium tuberculosis was grown from sputum and skin biopsy samples. Isoniazid, rifampin and pyrazinamide treatment for 2 months, followed by isoniazid and rifampin for 12 months, resulted in complete resolution. The clinical features of cutaneous tuberculosis in our patient were characteristic of tuberculous abscesses. Some uncommon findings, such as the low number of lesions, negative acid-fast resistant stains in cutaneous biopsy samples and his preserved general state of health, may be explained by a higher competence of the immune system than is usual in this clinical subset of disseminated tuberculosis. Cutaneous tuberculosis should be included in the differential diagnosis of cutaneous abscesses in immunocompetent patients.

Tuberculids represent a form of hypersensitivity reaction to tuberculosis antigens released from a distant focus of infection. Most patients are characterized by displaying a markedly positive Mantoux skin test and evidence of past tuberculosis infection or contacts of patients with tuberculosis. The treatment is based on tuberculin desensitizing therapy,antituberculosis drugs and corticosteroids.

This review is a synthesis and analysis of our nine experimental pathology papers on macrophage kinetics in dermal tuberculous lesions produced in rabbits by BCG. It is presented at this time to summarize the macrophage kinetics in both active and essentially healed tuberculous lesions and to suggest that the bacilli frequently multiply and are destroyed in the viable granulation tissue of many small arrested tuberculous lesions. The turnover of mononuclear cells (MN)-which were mostly macrophages with some medium and large lymphocytes-was most rapid in BCG lesions at 2-3 weeks (when tuberculin sensitivity and acquired cellular resistance were at their peaks). At this time, more macrophages entered, more died or left, more remained at the site, and more became activated than before or afterwards. Before this time, the host had no delayed-type hypersensitivity (DTH) and cell-mediated immunity (CMI), so that no antigen-specific enhancement of the inflammatory response occurred. After this time, the bacilli and their antigenic products had decreased, so that the stimuli for cell infiltration and activation were reduced. In "healed" lesions, the MN turnover still occurred, but was decreased. The continuous entry of live non-activated macrophages into the viable parts of tuberculous lesions provides fresh intracellular sites where tubercle bacilli may multiply before they are again inhibited by the DTH and CMI of the host. In tuberculosis, bacillary dormancy of long duration may only be present in caseous necrotic tissue where no live host cells exist.

We report on a 31-year-old female patient with systemic lupus erythematosus (SLE) for 24 years who had a past history of skin tuberculosis (lupus vulgaris), long-term corticosteroid therapy, and IgG deficiency. She presented with monoarthritis and concomitant meningitis from skin tuberculosis after 5 years. The diagnosis of joint and meningeal tuberculosis was defined with clinical symptoms--signs and typical histopathological findings of involved synovium. Clinical improvement was achieved with antituberculous therapy. Cutaneous, articular, and cerebral manifestations of tuberculosis might have been confused with some of the lupus manifestations or lupus activation. It should be kept in mind that tuberculosis may be encountered in SLE due to the nature of the underlying disease and/or its therapy. It is also worth mentioning that, in this patient, tissues involved with extrapulmonary tuberculosis were the primary areas of involvement with SLE.

We report a case of an unusual form of cutaneous tuberculosis in an 82-year-old woman. She visited our hospital because of an intractable ulcer on the fifth finger of her right hand. While examining the ulcer surrounding half of her right fifth finger and covered with necrotic tissue, we also perceived a nodule with crust on the forearm, multiple subcutaneous nodules on the right forearm and upper arm, and a hen's-egg-sized agglomerative nodule on the axilla. All the lesions were located on her right arm. Skin biopsy specimens showed granulomatous tissue with necrosis in the lesions. Mycobacterium tuberculosis was identified by culture of a biopsied specimen, so the diagnosis was confirmed. Further examination revealed that she also had pulmonary tuberculosis. Cutaneous tuberculoses are classified morphologically with reference to host immune status, but no satisfactory classification exists. The present case can't be classified into any of the types which have been proposed so far. She is elderly and suffers from liver cirrhosis, hepatocellular carcinoma and myelodysplastic syndrome. The resulting acquired immunosuppression may have caused a unique form of cutaneous tuberculosis.

Two patients came to their general practitioner for relatively minor problems: a 4-year-old boy came with a red eye and a 10-year-old girl with red foot soles. They came from Pakistan and Vietnam respectively. Their symptoms were due to tuberculosis, which diagnosis was established by Mantoux test and culture of a stomach aspirate. They were treated accordingly with isoniazid, rifampicin and pyrazinamide and with isoniazid, rifampicin and ethambutol respectively. These cases stress the importance of knowledge of the extrapulmonary manifestations of tuberculosis. As treatment exists and adequate treatment can diminish the reservoir of tuberculosis bacteria, early diagnosis can prevent the morbidity, spread and mortality of tuberculosis.

Orificial tuberculosis is a rare form of cutaneous tuberculosis. It happens mainly in immunocompromised patients and is characterized by rapidly ulcerating papules in the orifices, including oropharynx or anus, due to autoinoculation of internal tuberculosis. It is a symptom of advanced underlying disease. Kaposi's sarcoma occurs more frequently with the increase of HIV-infected patients. We report on an HIV-negative individual who developed rapid-deteriorating orificial tuberculosis concomitant with Kaposi's sarcoma and had a fatal outcome.

Primary cutaneous infections with MAC are extremely rare. We report a case of primary cutaneous infection with MAC, in a 69 year-old HIV-negative male. Idiopathic CD4+ T-lymphocytopenia was diagnosed.

We report the case of a 27-year-old patient with the human immunodeficiency virus (HIV) infection who presented with a 2-week history of crops of painful, red papules over the trunk and extremities, together with a sterile, symmetric polyarthritis involving the small and large joints. Histologic study of a skin biopsy specimen demonstrated features of papulonecrotic tuberculid. Analytical and microbiologic studies ruled out tuberculous infection. Both the synovial and the skin processes were considered to be an immune response secondary to Mycobacterium tuberculosis infection. Specific treatment was established, and there was marked improvement in both the skin and joint symptoms. This case illustrates the complex relationship between the host and the HIV, suggesting an immune dysregulation cause for both the synovial and the skin lesions.

To our knowledge, this is the first sequential study of cytokines in tissue sections of developing and healing tuberculous (BCG) lesions. In situ hybridization, immunohistochemical, and RT-PCR techniques were used. Cytokine mRNAs showed a biphasic pattern. The percentage of mononuclear cells (MN) containing IL-1beta, TNF-alpha, MCP-1, and IL-8 mRNAs was highest in 1- to 3-day lesions, apparently because of the nonspecific inflammatory response caused by the tubercle bacilli in the BCG vaccine. At 5 days, this percentage was significantly reduced. With IFN-gamma, the peak and trough were delayed by 2 days. By 9 days, the percentage of MN containing the mRNAs of all five cytokines had again increased and the rabbits had become tuberculin-positive. In general, MCP-1 and TNF-alpha proteins and the vascular adhesion molecules, ICAM, VCAM, and perhaps ELAM, peaked at about 3 days. Many mononuclear cells surrounding the central areas of solid and liquefied caseous necrosis contained chemokine IL-8 mRNA. IL-8 is known to attract PMN, and PMN were present nearby. In contrast, MN containing chemokine MCP-1 mRNA were present more peripherally in areas rich in macrophages and lymphocytes. The early nonspecific cytokine response seems to be an adjuvant effect of the mycobacteria in BCG vaccine in that it causes a rapid entry of macrophages, lymphocytes, granulocytes, and probably dendritic cells into local sites of antigen deposition. This effect should be considered in developing improved vaccines for the prevention of tuberculosis, because BCG vaccines producing a strong early cytokine response should be more immunogenic than BCG vaccines with similar antigens producing a weak response.

The granulomas of lupus vulgaris (LV) were characterized by preponderance of CD4+ lymphocytes and a raised CD4+/CD8+ ratio. In contrast, in scrofuloderma (SF) the CD8+ T-lymphocyte subpopulation predominated and the CD4+/CD8+ ratio was significantly decreased. A higher percentage of lymphocytes expressed interleukin-2 receptor (IL-2R) in LV as compared with SF, indicating an activated cellular immune response in the former. Immunophenotypic changes in tuberculosis verrucosa cutis (TBVC) were intermediate between LV and SF. CD4+ lymphocytes were the main infiltrating T-cell type in borderline tuberculoid leprosy (BT), while CD8+ lymphocytes predominated in the granuloma of lepromatous lepromatous (LL). The CD4+/CD8+ ratio and percentage of lymphocytes expressing IL-2R was significantly higher in BT as compared with LL. These immunophenotypic findings suggest that in both cutaneous tuberculosis and leprosy there is a continuous spectrum with regard to cell-mediated immunity depending on the clinical presentation.

Granulomas of lupus vulgaris were characterized by a raised CD4+/CD8+ ratio, while in scrofuloderma this was significantly decreased. Tuberculosis verrucosa cutis showed intermediate changes. These immunological variations suggest that cutaneous tuberculosis forms a spectrum with strong cell-mediated immunity seen in lupus vulgaris, and weaker cell-mediated responses in scrofuloderma; tuberculosis verrucosa cutis is intermediate between the two.