Tuberculosis heralding connective tissue disorder.

Connective tissue diseases and infections are amongst the causes for organising pneumonia. However, organising pneumonia preceding other connective tissue disease manifestations is rare. Mycobacterium tuberculosis is rarely associated with organising pneumonia. We report such a case. A 50-year-old diabetic male, a roadside shop keeper, a current smoker presented with fever, breathlessness, cough and weight loss for four months. Chest radiography demonstrated areas of consolidation with halo signs. Anti-nuclear antibody blot was positive for Scl-70 and Jo-1 suggestive of a syndrome of systemic sclerosis and polymyositis overlap. Fibre-optic bronchoscopy guided lung biopsy was suggestive of organising pneumonia, and broncho-alveolar lavage detected Mycobacterium tuberculosis. Mycobacterium tuberculosis should be investigated as an aetiology of organising pneumonia, as this may occur in unestablished cases of connective tissue disease even before clinical and radiological manifestations appear, as response can be achieved with anti-tuberculosis therapy alone, without additional use of systemic steroids.

A cluster of non-tuberculosis mycobacterial infections in patients with connective tissue diseases / Clúster de infecciones por micobacterias no tuberculosas en pacientes con enfermedad del tejido conectivo

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Current Treatment Options for Acute Skin and Skin-structure Infections.

Acute bacterial skin and skin-structure infections (ABSSSIs) are a common reason for seeking care at acute healthcare facilities, including emergency departments. Staphylococcus aureus is the most common organism associated with these infections, and the emergence of community-associated methicillin-resistant Staphylococcus aureus (MRSA) has represented a considerable challenge in their treatment. To address this need, a number of new antibiotics have been developed for the treatment of ABSSSIs in the past several years. Most of these agents focus primarily on gram-positive organisms, particularly MRSA; however, there has not been an oral agent that can reliably treat MRSA, as well as relevant gram-negative pathogens. Acute skin infections that involve mixed gram-positive and gram-negative pathogens must also be considered as they can be associated with discordant antimicrobial therapy. Here, I review ABSSSI treatment guidelines in the hospital setting and discuss current and future antibiotic options for treatment of this commonly encountered infection.

Evaluation of the multiplex PCR based assay Unyvero implant and tissue infection application for pathogen and antibiotic resistance gene detection in children and neonates.

BACKGROUND: Skin and soft tissue infections have a high disease burden in children. The emergence of multidrug-resistant bacteria over the last decades has heavily influenced hospitalization rates, morbidity and mortality. In addition, with increased survival rates in neonatology and oncology, health-care associated infections are more frequently encountered. There is a growing need for fast and feasible diagnostic tools for the recognition of microorganisms and drug resistances. METHODS: In this prospective study, we compared results of routine culture with the multiplex PCR based Unyvero Implant and Tissue Infection (ITI) application. Specimens were obtained from different sources from neonates and children. RESULTS: We analyzed specimens from 29 patients (72.4% male) with a median age of 8.1 years (range 0.03-15.2). Concordance between Unyvero ITI and culture was reached in 16 of 29 samples (55.2%). Unyvero ITI yielded an overall sensitivity and specificity of 76.3% and 96.5%, respectively. Accuracies were best for non-fermenting bacteria, for which sensitivity was 100% and specificity 98.2%. Detection rates were lower for Gram-positive bacteria (68.8 and 95.2%, respectively). Unyvero correctly detected one blaOXA-24/40 producing Acinetobacter baumannii, while none of the six gyrA87 had a correlate in antimicrobial susceptibility testing. CONCLUSIONS: Unyvero ITI quickly provides additional information relevant for clinical decision-makers. Sensitivity of the PCR must be improved especially for Gram-positive bacteria, and further studies are needed to assess the impact on clinical decision-making and outcome.

Differences in clinical Pneumocystis pneumonia in rheumatoid arthritis and other connective tissue diseases suggesting a rheumatoid-specific interstitial lung injury spectrum.

To compare Pneumocystis pneumonia (PCP) in patients with rheumatoid arthritis (RA) with PCP in patients with non-RA connective tissue diseases (CTDs) in order to clarify the characteristics of the former. We extracted consecutive patients satisfying the following criteria for "clinical PCP": (1) positive plasma ß-D-glucan, (2) PCP-compatible computed tomography findings of the lung, and (3) successful treatment with antipneumocystic antibiotics. Patients who underwent methylprednisolone "pulse" therapy or sufficient antibiotics to cure bacterial pneumonia were excluded. We used the t test, U test, or Fischer's exact probability test to compare the two groups and Jonckheere-Terpstra's test and Ryan's procedure for the trend test. Thirty-five cases were extracted. The underlying rheumatic diseases were RA in 25 and non-RA CTDs in ten. At the onset of clinical PCP, the lymphocyte counts were 884 vs 357/mm3 (p < 0.001), PC-PCR positivity 64% vs 100% (p = 0.029), glucocorticoid dose 4.0 vs 17.5 mg PSL/day (p < 0.001), and methotrexate dose 8 vs 0 mg/week (p = 0.003). The PC-PCR-negative patients, observed only in the RA group, were all receiving methotrexate (MTX) therapy except one patient who was receiving high-dose prednisolone alone. All PC-PCR-positive patients were receiving glucocorticoid, TNF inhibitor, or a non-MTX immunosuppressant. No patient with MTX alone had positive PC-PCR results. Clinical PCP in RA patients differed from that in non-RA CTD patients and may be understood as only a part of the rheumatoid-specific interstitial lung injury spectrum influenced by multiple, synergistic factors including MTX, Pneumocystis, and RA itself.

The Microbiome in Connective Tissue Diseases and Vasculitides: An Updated Narrative Review.

OBJECTIVE: To provide a narrative review of the most recent data concerning the involvement of the microbiome in the pathogenesis of connective tissue diseases (CTDs) and vasculitides. METHODS: The PubMed database was searched for articles using combinations of words or terms that included systemic lupus erythematosus, systemic sclerosis, autoimmune myositis, Sjögren's syndrome, undifferentiated and mixed CTD, vasculitis, microbiota, microbiome, and dysbiosis. Papers from the reference lists of the articles and book chapters were reviewed, and relevant publications were identified. Abstracts and articles written in languages other than English were excluded. RESULTS: We found some evidence that dysbiosis participates in the pathogenesis of systemic lupus erythematosus, systemic sclerosis, Sjögren's syndrome, and Behçet's disease, but there are still few data concerning the role of dysbiosis in other CTDs or vasculitides. CONCLUSIONS: Numerous studies suggest that alterations in human microbiota may be involved in the pathogenesis of inflammatory arthritides as a result of the aberrant activation of the innate and adaptive immune responses. Only a few studies have explored the involvement of dysbiosis in other CTDs or vasculitides, and further research is needed.

[The gastrointestinal tract microbiom in connective tissue diseases].

Factors such as genetics, the environment, infections, and the human body microbiota, mainly gastrointestinal tract microbiota may play a role in the pathogenesis of autoimmune disorders. There is an increasing evidence that suggest an association between gastrointestinal tract dysbiosis, and in particular gut dysbiosis, and connective tissue diseases but it still remains unclear whether alterations in the microbiome are a pathogenic cause or an effect of autoimmune disease. Given the strong variability and abundance of microbes living in close relation with human host, it becomes a difficult task to define what should be considered the normal or the favorable microbiome. Further studies are needed to establish how the human microbiome contributes to disease susceptibility, and to characterize the role of microbial diversity in the pathogenesis of connective tissue diseases and their clinical manifestations. The identification of dysbiosis specific for certain connective tissue diseases may help in the development of an individualized management for each patient. This review aims to summarize current data on the role of the gastrointestinal tract microbiome in connective tissue diseases.

Rare case of subcutaneous mycosis with intrathoracic extension due to Chaetomium strumarium.

A 47-year-old man presented with a 10-year history of multiple lumps over his left upper arm and shoulder and the adjoining left side of his chest and upper back. His medical history included diabetes mellitus type 2. The patient was a farmer and used to lift sacks of grains and fertilizers onto his shoulders as part of his work, although he did not recollect any history of specific trauma. Skin biopsy revealed granulomatous reaction with Splendore-Hoeppli phenomenon, while periodic-acid-Schiff and Grocott-Gomori stains confirmed fungal elements. Sabouraud agar grew Chaetomium species, and lactophenol blue mount confirmed the fungus as Chaetomium strumarium. Radiography and computed tomography of the chest revealed intrathoracic extension of the mycetoma. The patient responded well to treatment with oral Itraconazole. Subcutaneous mycosis due to C. strumarium is rarely reported in the literature, and the intrathoracic extension makes it an even rarer entity.

[Acral necrosis as a complication of urosepsis]. / Akrale Nekrosen als Komplikation einer lithogenen Urosepsis.

Sepsis is the third most common cause of death in Germany. Every fourth patient with sepsis has urosepsis. Even if substantial therapeutic progress has been made, sepsis remains a severe condition with high morbidity and mortality that requires rapid interdisciplinary measures. Besides life-threatening complications, acral necrosis as presented here can occur as a result of disseminated intravascular coagulation and severe microcirculatory disorders.

Efficacy and safety of liposomal amphotericin B for deep mycosis in patients with connective tissue disease.

The efficacy and safety of liposomal amphotericin B (L-AMB) in the treatment of invasive fungal infections (IFIs) were retrospectively evaluated for patients with connective tissue diseases (CTDs) during treatment with immunosuppressive therapy. Subjects were 13 patients with CTDs complicated by IFI, on the basis of clinical symptoms, imaging findings, and microbiological and histological examinations. All patients were treated with L-AMB. Efficacy and safety were evaluated before and after administration of L-AMB. Underlying diseases were systemic lupus erythematosus for 4 patients, rheumatoid arthritis for 3, microscopic polyangiitis for 2, adult-onset Still disease for 1, dermatomyositis for 1, and mixed connective tissue disease for 1. Eight patients were resistant to other antifungal drugs. Prednisolone was given to 11 patients and the median dose was 10 mg/day. Immunosuppressants were used for 8 patients. The median duration of administration of L-AMB was 8.5 days (range 4-38 days). In proven and probable diagnosis patients (n = 5), the treatment was effective for 3 patients and ineffective for 2 (efficacy rate 60 %). Serum 1,3-ß-D-glucan antigenemia (BG) levels decreased after treatment in the 2 patients who were positive for BG. Serum Aspergillus galactomannan antigen levels decreased in 3 of 4 patients with Aspergillus infection. No patient died of IFI. Regarding potential adverse reactions, there were no significant changes in serum creatinine and potassium levels. L-AMB is effective and well-tolerated for treatment of IFI in patients with CTDs.

Normal human gingival epithelial cells sense C. parapsilosis by toll-like receptors and module its pathogenesis through antimicrobial peptides and proinflammatory cytokines.

This study was designed to investigate the interaction between C. parapsilosis and human epithelial cells using monolayer cultures and an engineered human oral mucosa (EHOM). C. parapsilosis was able to adhere to gingival epithelial cells and to adopt the hyphal form in the presence of serum. Interestingly, when cultured onto the engineered human oral mucosa (EHOM), C. parapsilosis formed small biofilm and invaded the connective tissue. Following contact with C. parapsilosis, normal human gingival epithelial cells expressed high levels of Toll-like receptors (TLR)-2, -4, and -6, but not TLR-9 mRNA. The upregulation of TLRs was paralleled by an increase of IL-1beta, TNFalpha, and IFNgamma mRNA expression, suggesting the involvement of these cytokines in the defense against infection with C. parapsilosis. The active role of epithelial cells in the innate immunity against C. parapsilosis infection was enhanced by their capacity to express high levels of human beta-defensin-1, -2, and -3. The upregulation of proinflammatory cytokines and antimicrobial peptide expression may explain the growth inhibition of C. parapsilosis by the gingival epithelial cells. Overall results provide additional evidence of the involvement of epithelial cells in the innate immunity against C. parapsilosis infections.

Bilateral Staphylococcus aureus sub-Tenon's abscess following strabismus surgery in a child.

Infection after strabismus surgery is rare. Here we describe a 5-year-old girl who developed bilateral staphylococcal sub-Tenon's abscess resistant to fourth-generation fluoroquinolones that resolved completely after surgical drainage and irrigation with povidone iodine followed by administration of oral amoxicillin and clavulanic acid. A lost muscle required exploration and reattachment to the sclera.

Infections, connective tissue diseases and vasculitis.

In genetically predisposed individuals, viruses, bacteria, or parasitic infectious agents are suspected of inducing autoimmunity and/or exacerbating autoimmune rheumatic diseases (ARD) once self-tolerance is broken. Although direct evidence for this association is still lacking, numerous data from animal models as well as from humans support the hypothesis of a direct contribution of pathogens to the induction of several ARD. This review focuses on the possible role of infectious agents as triggers of autoimmunity in systemic lupus erythematosus, polymyositis-dermatomyositis, antiphospholipid antibody syndrome, and primary vasculitis. Indeed, vasculitis may be a clinical manifestation of an infectious disease (secondary vasculitis). In addition, immune response abnormalities and immunosuppressive medications may be responsible for the high percentage of infectious complications in ARD patients. Recent therapeutic approaches aimed at lowering doses of cytotoxic agents and shortening duration of treatment with the most toxic drugs, have proved to be as effective as conventional regimens. New drugs and strategies aimed at preventing infections could further improve the outcome of ARD patients.

[Microflora in patients with systemic connective tissue diseases].

The study of microflora of skin, mucous tunic of nose and mouth, and the quantitative and qualitative structure of the intestinal and urinal microflora in cases of systemic connective tissues diseases, are reproduced. The decrease of the dominant state of typical representatives, and the increase of the role of pseudopathogenic bacteria in various biotypes, were observed. The frequency of S. aureus detection increased in skin, mucous tunic of nose and mouth. Pseudopathogenic microbes acquired greater significance in the forming of microbiocenosis of intestine, while the number of E. coli, Bifidobacterium and Lactobacterium decreased. The frequency of detection of microbes in urine decreased. The comparative analyses of the microflora in patients with systemic lupus erythromatosis and progressive systemic sclerosis demonstrated the common peculiarities for microflora character change.

[Intestinal microbiocenosis in systemic connective tissue diseases].

The purpose of the investigation was to study the quantitative and qualitative composition of colon microflora in system connective tissue diseases and system vasculites. The authors studied colon microflora in patients with systemic lupus erythematosus, systemic scleroderma, nodular polyarteritis, and hemorrhagic vasculitis. The structure of symbiotic interrelations between microorganisms participating in the formation of colon microbiocenosis was determined. Colon microflora was found to be disordered in terms of its qualitative and quantitative composition. The predomination of anaerobic microorganisms was decreased, while the role of conditionally pathogenic bacteria was increased. The number of lactobacteria was significantly lowered; bifidobacteria and bacteroids were found frequently, while their number was substantially lowered as well. Conditionally pathogenic microorganisms and bacteria with hemolytic activity acquired high significance in the forming of the colon microbiocenosis of the patients. The frequency of the isolation and the density of colon colonization with staphylococci and conditionally pathogenic enterobacteria were significantly increased. General trends and peculiarities of changes in the quantitative and qualitative composition of colon microflora in some rheumatic diseases were determined. The data on the peculiarities of the colon microbiocenosis in these patients may be used to substantiate methods of complex therapy including correction of dysbiotic disturbances.

[Auricular perichondritis in adults. An evaluation-study of 12 hospitalized patients]. / Pericondritis del pabellón auricular en adultos. Estudio-evaluación de 12 pacientes ingresados.

Perichondritis of the auricle in adults can be secondary to traumatic agents, external otitis or surgery being Pseudomona aeruginosa the bacteria more often isolated. We have performed a retrospective study of 12 hospitalized patients with that diagnosis and these following variables have been evaluated: Age, sex, personal antecedents, clinical symptoms, affected auricle, complementary explorations, treatment, evolution and stay.

Pericondritis del pabellón auricular en adultos / An evaluation-study of 12 hospitalized patients

Las pericondritis que afectan al pabellón auricular en adultos pueden ser debidas a traumatismos, otitis externas o cirugía, siendo Pseudoma aeruginosa la bacteria responsable más comúnmente aislada. Realizamos un estudio retrospectivo de 12 pacientes ingresados con este diagnóstico en el que evaluamos las siguientes variables: edad, sexo, antecedentes personales, sintomatología clínica, pabellón afecto, exploraciones complementarias, tratamiento evolución y estancia hospitalaria

Perichondritis of the auricle in adults can be secondary to traumatic agents, external otitis or surgery being Pseudomona aeruginosa the bacteria more often isolated. We have performed a retrospective study of 12 hospitalized patients with that diagnosis and these following variables have been evaluated: Age, sex, personal antecedents, clinical symptoms, affected auricle, complementary explorations, treatment, evolution and stay

An unusual localization of mucormycosis diagnosed by fine needle aspiration cytology: a case report.

Mucormycosis is an uncommon fungal infection, occurring mainly in patients with acidosis, chronic illnesses and malignancies. The most frequent site of involvement in patients of hematological malignancies is the respiratory tract. Isolated subcutaneous localization of mucormycosis in such patients is extremely rare. We report a case of a young patient of non-Hodgkin's lymphoma on chemotherapy who presented with a subcutaneous swelling on the anterior aspect of right thigh. Fine needle aspiration cytology (FNAC) smears from the swelling revealed numerous characteristic broad, irregularly contoured and pleomorphic hyphae of mucormycosis. This fungus seldom grows in culture and confirmation of the diagnosis depends on cytological or histological examination of infected tissues. Our case report documents a rare site of isolated mucormycosis infection and emphasizes the role of FNAC as a simple, rapid, accurate, and useful method of diagnosing fungal infections.

Hand infections: basic principles and management.

BACKGROUND: An untreated hand infection can lead rapidly to tissue destruction and permanent disability. METHODS: Review of the pertinent English literature. RESULTS: Early diagnosis and timely, effective intervention is crucial to treatment. Anatomically, the hand consists of multiple potential spaces and tissue planes that can become infected with a wide variety of organisms. Thus, a working knowledge of hand anatomy as well as pharmalogical therapies is imperative for successful management. CONCLUSIONS: Knowledge of the basic principles of hand care, relevant anatomy, infectious organisms, and clinical signs of an unusually aggressive infection greatly improves treatment efficacy.

[Microflora of the large intestine in patients with connective tissue dysplasia]. / Mikroflora tolstoi kishki u patsientov s displaziei soedinitel'noi tkani.

The specific features of intestinal aerobic and anaerobic intestinal microflora in children with nondifferentiated connective tissue dysplasia were under study. A high rate of dysbiotic disturbances was noted in patients with connective tissue dysplasia in comparison with healthy persons. Profound quantitative and qualitative changes in the biocenosis of the intestine were detected in patients with the pathology of the gastrointestinal tract as well as that of the locomotor system. Changes in the species composition and the persistence properties of the intestinal microflora may serve as pathogenetic factors in the development of connective tissue dysplasia.