Arthroscopic treatment of Mycobacterium massiliense septic arthritis outbreak after intra-articular injection: A case-series report and literature review.

ABSTRACT: Non-tuberculous mycobacteria (NTM) comprise mycobacteria, with the exceptions of Mycobacterium (M.) leprae and the M. tuberculosis complex. Septic arthritis caused by NTM is so rare that there is no standardized treatment.Between April and September 2012, 27 patients were infected with M. massiliense in a single clinic following injection of steroid in the knee joint. Clinical data of 9 patients who received arthroscopic treatment in Seoul Hospital of Soonchunhyang University were analyzed retrospectively.Arthroscopic irrigation and debridement were performed average 2.6 times (1-3 times). As 6 out of 9 cases (67%) had joint contracture of the knee joint, arthroscopic adhesiolysis, and brisement were performed. After surgical procedures, Hospital for Special Surgery and Lysholm knee score showed improvement compared before the surgery, but a radiographic result evaluated by Kellgren-Lawrence revealed that 6 cases got deteriorated to stage 4 in the 4-year follow-up.NTM septic arthritis had a higher recurrence and a higher contracture incidence than septic arthritis caused by tuberculous mycobacteria or other bacteria. Treatment was possible with repeated arthroscopic debridement and intravenous antibiotics.

Vaping Associated Pulmonary Nontuberculous Mycobacteria.

INTRODUCTION: E-cigarette or vaping product use associated lung injury (EVALI) has been an important health risk in both children and adults. The pathophysiology of EVALI is not well understood. However, it is speculated that certain substances such as Vitamin E Acetate (VEA), particularly in marijuana containing vape cartridges may result in lung injury and lead to respiratory dysfunction. EVALI is often seen in the absence of infections, but it has been found to be associated with both fungal and bacterial infections. Like EVALI, nontuberculous mycobacteria (NTM) pulmonary disease is also on the rise, but is primarily reported in immunocompromised individuals. Here, we present three immunocompetent individuals wherein pulmonary NTM infection co-occurred with vaping. METHODS: Medical information including patient history, laboratory, and radiograph reports were abstracted from electronic medical records from participating institutions located in the Bronx, NY, Philadelphia, PA, and Lexington, KY. RESULTS: All three cases were otherwise immunocompetent individuals with a significant history of vaping either nicotine and/or marijuana containing products. The pathogens isolated include Mycobacterium avium complex, M. xenopi, and M. gordonae. All three patients were treated for NTM. CONCLUSION: There is little reported on the association between vaping and NTM. It is possible that vaping may have rendered these individuals to be more susceptible to NTM colonization and infection. The possible mechanisms of vaping lung injury and pulmonary NTM are discussed.

Mycobacterial Infections Potentiated by Biologics.

Biologic therapies have revolutionized the treatment of immune-mediated inflammatory diseases but are associated with an increased risk of serious and opportunistic infections, including tuberculosis and nontuberculous mycobacterial disease. Despite this increased risk, the overall risk-benefit ratio remains favorable with appropriate screening and risk assessment. Further population-based studies are needed to establish the risk of tuberculosis and nontuberculous mycobacterial disease with the new biologics. This article highlights the incidence and drug-specific risk of tuberculous and nontuberculous mycobacterial infection in the setting of biologics, screening and prevention, and treatment of latent tuberculosis in this setting.

Disseminated Bacillus Calmette-Guérin (BCG) infection with pulmonary and renal involvement: A rare complication of BCG immunotherapy. A case report and narrative review.

Intravesical Bacillus Calmette-Guérin (BCG) instillation is a mainstay of adjunctive therapy for superficial bladder cancer that increases length of disease progression-free survival. Although usually well tolerated, moderate to severe local and systemic infectious complications can occur with this immunotherapy. Diagnosis is difficult and often based on high clinical suspicion since in many cases Mycobacterium bovis is not isolated. Treatment is not fully standardized but the combination of anti-tuberculosis drugs and corticosteroids is advocated in severe cases. The authors present an unusual case of a severe infectious complication following intravesical BCG instillation with pulmonary and kidney involvement. Prompt anti-tuberculosis treatment associated to corticosteroid resulted in a marked clinical and radiological improvement, supporting the diagnosis of disseminated BCG infection. Based on this, the authors aimed to review the literature on this exceptional complication of this immunotherapy.

Mycobacterial Infections With Ruxolitinib: A Retrospective Pharmacovigilance Review.

BACKGROUND: Ruxolitinib is a selective Janus kinase inhibitor (JAKI) 1/2 approved for the treatment of myelofibrosis (MF) and polycythemia vera (PV). These patients may be at risk for developing opportunistic infections. We assessed the number of patients that developed typical (Mycobacterium tuberculosis [MTB]) and atypical mycobacterial infections (AMI) while on treatment with ruxolitinib by utilizing the United States Food and Drug Administration (FDA) adverse events reporting system (FAERS). MATERIALS AND METHODS: This is a retrospective study utilizing FAERS, a pharmacovigilance database. We queried FAERS for cases of MTB and AMI secondary to ruxolitinib between January 1, 2011 and December 31, 2018. Disproportionality signal analysis was done by calculating the reporting odds ratio (ROR). ROR was considered significant when the lower limit of 95% confidence interval (CI) was > 1. RESULTS: There were 91 reported cases of MTB associated with ruxolitinib compared with 4575 cases from all other drugs. The ROR was significant at 9.2 (95% CI, 7.5-11.4). There were 23 reports of AMI with ruxolitinib compared with 1287 reported with all other drugs. The ROR was significant at 8.3 (95% CI, 5.5-12.6). Twelve (13.2%) patients with MTB and 8 (34.8%) with AMI died. CONCLUSION: Patients on ruxolitinib are at increased risk of developing MTB and AMI. Clinicians should be aware of this risk and consider screening patients for latent MTB prior to initiating ruxolitinib.

Opportunistic Infections in Biological Therapy, Risk and Prevention.

Patients being treated with biological therapies are at increased risk for serious infections, including opportunistic infections. Although more is known about opportunistic infection risk with older biologics, such as antitumor necrosis factor drugs, there is less knowledge of opportunistic infection risk with newer biological therapies. The incidence of certain opportunistic infections (tuberculosis, herpes zoster, pneumocystosis) has been rigorously evaluated in large observational studies. However, data are more limited for other infections (histoplasmosis, nontuberculous mycobacteria). Infectious morbidity and mortality may be preventable with screening and prophylaxis in select populations.

Mycobacterium marinum infection contracted from seaweed wrap in a psoriasis patient undergoing treatment with adalimumab.

We report a patient with psoriasis who developed Mycobacterium marinum (M. marinum) infection after seven years of treatment with adalimumab, a human anti-TNF (tumor necrosis factor) monoclonal antibody. TNF is a pro-inflammatory cytokine that plays a central role in the pathogenesis of psoriasis and a number of other immune-mediated inflammatory diseases. TNF plays an important role in granuloma formation and host defense against mycobacterial infections. Several cases of atypical mycobacterial infections in patients on TNF inhibitors have been reported. To our knowledge, this is the second reported case of M. marinum infection in a patient on adalimumab for the treatment of psoriasis.

Increased risk of mycobacterial infections associated with anti-rheumatic medications.

RATIONALE: Anti-tumour necrosis factor (TNF) agents and other anti-rheumatic medications increase the risk of TB in rheumatoid arthritis (RA). Whether they increase the risk of infections with nontuberculous mycobacteria (NTM) is uncertain. OBJECTIVES: To determine the effect of anti-TNF therapy and other anti-rheumatic drugs on the risk of NTM disease and TB in older patients with RA. METHODS: Population-based nested case-control study among Ontario seniors aged ≥67 years with RA who were prescribed at least one anti-rheumatic medication between 2001 and 2011. We identified cases of TB and NTM disease microbiologically and identified drug exposures using linked prescription drug claims. We estimated ORs using conditional logistic regression, controlling for several potential confounders. MEASUREMENTS AND MAIN RESULTS: Among 56 269 older adults with RA, we identified 37 cases of TB and 211 cases of NTM disease; each case was matched to up to 10 controls. Individuals with TB or NTM disease were both more likely to be using anti-TNF therapy (compared with non-use); adjusted ORs (95% CIs) were 5.04 (1.27 to 20.0) and 2.19 (1.10 to 4.37), respectively. Exposure to leflunomide and other anti-rheumatic drugs with high immunosuppressing potential also were associated with both TB and NTM disease, while oral corticosteroids and hydroxychloroquine were associated with NTM disease. CONCLUSIONS: Anti-TNF use is associated with increased risk of both TB and NTM disease, but appears to be a relatively greater risk for TB. Several other anti-rheumatic drugs were also associated with mycobacterial infections.

A case of opportunistic skin infection with Mycobacterium marinum during adalimumab treatment in a patient with Crohn's disease.

Opportunistic infections, especially reactivation with M. tuberculosis, are major complications during treatment with anti-TNF agents. Infections with atypical mycobacteria like Mycobacterium marinum are rare and tend to turn into a difficult and prolonged course due to delayed diagnosis. This is the first case of M. marinum infection during adalimumab therapy in a patient with Crohn's disease. The most important diagnostic step was a detailed medical history as PCR tested for M. tuberculosis and for atypical subspecies was false negative. Up to now a discontinuation of anti-TNF therapy has been recommended, however, there is no consensus about the reintroduction of biologicals after sufficient anti-infective therapy. In this patient anti-TNF therapy had to be reintroduced because of increasing activity with no relapse of M. marinum after a follow-up of 12 months.

Chronic respiratory disease, inhaled corticosteroids and risk of non-tuberculous mycobacteriosis.

BACKGROUND: Chronic respiratory disease and inhaled corticosteroid (ICS) therapy for chronic obstructive pulmonary disease (COPD) increase the risk of pneumonia. Few data are available on the association of these risk factors with non-tuberculous mycobacterial (NTM) pulmonary disease. METHODS: This study examined chronic respiratory diseases and ICS use as risk factors in a population-based case-control study encompassing all adults in Denmark with microbiologically confirmed NTM pulmonary disease between 1997 and 2008. The study included 10 matched population controls per case. Conditional logistic regression was used to compute adjusted ORs for NTM pulmonary disease with regard to chronic respiratory disease history. RESULTS: Overall, chronic respiratory disease was associated with a 16.5-fold (95% CI 12.2 to 22.2) increased risk of NTM pulmonary disease. The adjusted OR for NTM disease was 15.7 (95% CI 11.4 to 21.5) for COPD, 7.8 (95% CI 5.2 to 11.6) for asthma, 9.8 (95% CI 2.03 to 52.8) for pneumoconiosis, 187.5 (95% CI 24.8 to 1417.4) for bronchiectasis, and 178.3 (95% CI 55.4 to 574.3) for tuberculosis history. ORs were 29.1 (95% CI 13.3 to 63.8) for patients with COPD on current ICS therapy and 7.6 (95% CI 3.4 to 16.8) for patients with COPD who had never received ICS therapy. Among patients with COPD, ORs increased according to ICS dose, from 28.1 for low-dose intake to 47.5 for high-dose intake (more than 800 µg/day). The OR was higher for fluticasone than for budesonide. CONCLUSION: Chronic respiratory disease, particularly COPD treated with ICS therapy, is a strong risk factor for NTM pulmonary disease.

Radiological features and therapeutic responses of pulmonary nontuberculous mycobacterial disease in rheumatoid arthritis patients receiving biological agents: a retrospective multicenter study in Japan.

OBJECTIVE: This study was performed to evaluate the radiological features of and therapeutic responses to pulmonary disease caused by nontuberculous mycobacteria (NTM) in the setting of biological therapy for rheumatoid arthritis (RA). METHODS: We conducted a retrospective chart review of 13 patients from multiple centers who had developed pulmonary NTM disease during biological therapy for RA, including infliximab, etanercept, adalimumab, and tocilizumab. RESULTS: Most cases were asymptomatic or resulted in only common-cold-like symptoms. Abnormalities in computed tomography (CT) imaging were protean and frequently overlapped. The most predominant pattern was nodular/bronchiectatic disease (six cases), followed by alveolar infiltrate (three cases), cavitary disease (two cases), and pulmonary nodules (two cases). In most cases, pulmonary NTM disease had spread from a preexisting lesion; in particular, bronchial/bronchiolar abnormalities. In three cases, one or more nodular lesions with or without calcification were a focus of disease. Following the discontinuation of biological agents, most patients responded to anti-NTM therapy. Two patients showed no exacerbation in the absence of any anti-NTM therapy. In one patient, restarting tocilizumab therapy while continuing to receive adequate anti-NTM therapy produced a favorable outcome. In two other patients with a previous history of pulmonary NTM disease, introducing biological therapy led to recurrence, but anti-NTM therapy was effective in these patients. CONCLUSION: CT abnormalities of pulmonary NTM disease in RA patients receiving biological therapy were variable, but were not unique to this clinical setting. NTM disease can spread from preexisting structural abnormalities, even if they are minute. Contrary to our expectations, the therapeutic outcomes of pulmonary NTM disease were favorable in these patients.

[A case of acute and necrotizing cutaneous Mycobacterium marinum infection in a patient treated with infliximab for Crohn's disease]. / Infection cutanée aiguë et nécrosante a Mycobacterium marinum chez un patient traité par infliximab pour une maladie de Crohn.

BACKGROUND: The increasing use of anti-TNFalpha exposes patients to emerging risks, particularly that of infection. We report a case of severe cutaneous Mycobacterium marinum infection in a patient treated with infliximab and we discuss therapeutic options. PATIENTS AND METHODS: A man treated with infliximab for Crohn's disease developed a severe cutaneous infection with M. marinum. Despite withdrawal of infliximab and the introduction of triple antibiotic therapy, the patient's lesions worsened and surgical treatment was required. DISCUSSION: The worsening experienced by our patient 1 week after the beginning of the treatment is comparable with the immune reconstitution syndrome occasionally observed in tuberculosis in immunocompromised hosts, thus raising the question of the potential value of continuing infliximab treatment. Recommendations are needed concerning the prevention and treatment of M. marinum infections in patients on anti-TNFalpha biotherapies.

Tuberculosis in the age of biologic therapy.

The introduction of biologic therapies for psoriasis has revolutionized the treatment of plaque psoriasis. These changes in our drug armamentarium have resulted in the need for dermatologists to have a through command of knowledge regarding tuberculosis given the potential for reactivation with this class of medications. The focus of this review is to update dermatologists on pertinent information regarding the microbiology, immunology, screening, and recognition of the clinical presentations of tuberculosis. The current literature regarding the occurrence of tuberculosis with biologics, specifically antitumor necrosis factor therapy, is reviewed. Special emphasis is placed on the different clinical presentations between newly acquired tuberculosis versus reactivation of latent disease while receiving these medications. Given the ever-widening use of biologic therapy in our specialty, we must be capable of rapidly identifying infected patients, including those with asymptomatic latent disease. The failure to screen for tuberculosis before the initiation of biologic therapy may result in adverse outcomes for both the patient and the overall health of our communities.

Understanding, avoiding, and managing dermal filler complications.

BACKGROUND Dermal fillers are increasingly being utilized for multiple cosmetic dermatology indications. The appeal of these products can be partly attributed to their strong safety profiles. Nevertheless, complications can sometimes occur. OBJECTIVE To summarize the complications associated with each available dermal filling agent, strategies to avoid them, and management options if they do arise. METHODS AND MATERIALS Complications with dermal fillers reported in peer-reviewed publications, prescribing information, and recent presentations at professional meetings were reviewed. Recommendations for avoiding and managing complications are provided, based on the literature review and the author's experience. RESULTS Inappropriate placement or superficial placement is one of the most frequent reasons for patient dissatisfaction. Due to the reversibility of hyaluronic acid, complications from these fillers can be easily corrected. Sensitivity to any of the currently approved FDA products is quite rare and can usually be managed with anti-inflammatory agents. Infection is quite uncommon as well and can usually be managed with either antibiotics or antivirals depending on the clinical features. The most concerning complication is cutaneous necrosis, and a protocol to treat the full spectrum of this process is reviewed. CONCLUSIONS Complications with dermal fillers are infrequent, and strategies to minimize their incidence and impact are easily deployed. Familiarity with each family of soft-tissue augmentation products, potential complications, and their management will optimize the use of these agents.

Mycobacterium marinum infection complicating Crohn's disease, treated with infliximab.

Tumour necrosis factor-alpha inhibitors including infliximab are often used to treat a number of recalcitrant medical conditions. These agents are increasingly associated with infections, particularly mycobacterial infections. We report sporotrichoid spread of Mycobacterium marinum in a 37-year-old woman with Crohn's disease, who had been receiving infliximab infusions for 2 years. An infection had spread up the right leg, after she had been swimming on holiday in the Canary Islands. M. marinum was cultured from the lesions and also identified by PCR on formalin-fixed tissue. To our knowledge, this is the first report of M. marinum occurring in a patient receiving infliximab.