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Amikacin liposome inhalation suspension (ALIS) is a key drug for the treatment of refractory Mycobacterium avium complex pulmonary disease (MAC-PD). Although cases of drug-induced interstitial lung disease (DIILD) by ALIS have been reported, its diagnosis is challenging due to overlapping existing pulmonary shadows, airway bleeding, exacerbation of underlying conditions, and the potential for various concurrent infections. A 72-year-old woman started treatment with ALIS for refractory MAC-PD. Three weeks later, she had a fever, cough, and appetite loss. She was hospitalized because multiple infiltrative opacities were observed on chest X-ray and chest computed tomography. Because the opacities worsened after empiric antibiotic therapy with broad-spectrum antibiotics, we initiated corticosteroid therapy, suspecting DIILD caused by ALIS, although drug lymphocyte stimulation tests for ALIS and amikacin were negative. Three days later, we found signs of improvement and quickly tapered the corticosteroids. After obtaining informed consent, we performed a drug provocation test of ALIS. Seven days later, she exhibited fever, an increased peripheral white blood cell count, and elevated serum C-reactive protein level, all of which returned to baseline 4 days after stopping ALIS, leading to a diagnosis of DIILD caused by ALIS in this patient. DIILD caused by ALIS is rare but should be carefully diagnosed to ensure that patients with refractory MAC-PD do not miss the opportunity to receive ALIS treatment.

Paradoxical inflammatory responses can occur during microbiologically successful antituberculous therapy. Optimal treatment is unknown, but corticosteroids are used most often. It is likely that interleukin-1 (IL-1) plays a central role in the development of these paradoxical responses, and if corticosteroids fail or are undesirable because of adverse effects, anti-IL-1 therapy may therefore be a rational choice.
We present seven HIV-negative tuberculosis patients with paradoxical responses, two with exclusively pulmonary and five with extrapulmonary tuberculosis. All had received corticosteroids, with unsatisfactory effect. Patients were treated with the IL-1 receptor antagonist anakinra and monitored for reduction of fever and inflammatory markers, imaging evidence of stabilization or regression of lesions, and respiratory improvement.
Six patients had anemia and four patients had lymphopenia at the start of the antituberculosis treatment. Fever was present in six patients at the moment of paradoxical response. Anakinra resulted in the decrease of fever within days, followed by resolution of symptoms and radiological improvement in five patients. Anakinra induced neutropenia, necessitating its cessation in two patients, who recovered quickly afterward.
Anakinra can be considered in HIV-negative tuberculosis patients with paradoxical responses when steroids fail or are undesired. Given its favorable safety profile and reversible side effects, it is conceivable that anakinra might also be used as first-line adjuvant treatment for paradoxical responses.
A.v.L. and R.v.C. are supported by National Institutes of Health (R01AI145781).

Emerging anti-tumor necrosis factor (TNF)-α antibodies therapy changed treatment strategy to inflammatory bowel diseases because of the efficacy. However, TNF-α inhibitor can be associated with an increased risk of infectious complications, especially tuberculosis. A 71-year-old female with steroid-dependent ulcerative colitis (UC) was admitted due to relapse of UC with endoscopically severe active. Golimumab and adjunctive prednisolone started with 30 mg daily resulted in clinical remission. However, she had general fatigue and fever at the time of seventh injection of golimumab without abdominal symptoms. Based on positive interferon-gamma release assay, polymerase chain reaction positive for tuberculosis (TB) in pleural fluid, and chest computed tomography, she was diagnosed as tuberculous pleuritis. Standard anti-TB treatment (isoniazid, rifampicin, ethambutol, and pyrazinamide) was started without cessation of golimumab, because cessation of TNF-α inhibitors during anti-TB treatment could cause the paradoxical response by skewing from regulatory to inflammatory immune responses. However, four weeks after initiation of anti-TB treatment, she got fever-up and pleural effusion increased. We then started prednisolone 30 mg daily as diagnosis of paradoxical response, resulting in improving the symptoms. This is a suggestive case of paradoxical response during anti-TB treatment despite continuous TNF-α inhibitors.

Antitumor necrosis factor-associated nontuberculous mycobacteria-immune reconstitution inflammatory syndrome (IRIS) has rarely been reported. An 84-year-old woman with a history of rheumatoid arthritis treated with etanercept was diagnosed with Mycobacterium avium complex (MAC) pulmonary disease six years before admission. Etanercept was discontinued two years ago because of MAC pulmonary disease progression and restarted nine months before admission because of worsening arthritis, again resulting in MAC pulmonary disease progression. Etanercept was discontinued again; however, the pulmonary disease progressed more rapidly. The condition was considered paradoxical worsening caused by IRIS due to etanercept discontinuation. The disease resolved quickly with chemotherapy for MAC.

Cerebral tuberculosis (TB) presents most frequently as meningitis in the basilar cistern; however, it can also manifest in various other ways, such as localized encephalitis, abscess, and tuberculoma. Here, focusing on imaging findings, we report an immunocompetent case who demonstrated multiple parenchymal lesions and was diagnosed with cerebral TB after testing positive on QuantiFERON (QTF); her clinical signs/symptoms and laboratory findings responded well to anti-TB medication therapy. The patient was a 60-year-old woman with the chief complaints of headache and consciousness disturbance. On admission, cerebrospinal fluid (CSF) examination showed increased monocyte predominance. T2-weighted images showed multiple, widely distributed hyperintense lesions in the periventricular and deep white matter. Gadolinium-enhanced three-dimensional gradient echo T1-weighed images revealed numerous granules or faint, small, enhanced foci in lesions in the periventricular and deep white matter, central gray matter, and hippocampus. Some abnormal sulcal enhancement was detected in the pia mater, indicating meningitis. Clinically, the diagnosis was difficult to make, but as the QTF result was positive, anti-TB drugs were administered, after which both the symptoms and CSF cell count showed improvement.

It can be difficult for clinicians to distinguish a paradoxical response to antituberculous therapy, worsening of an existing lesion despite adequate treatment, treatment failure, and drug resistance. We report a case of a 69-year-old woman who experienced bilateral lower extremity paralysis secondary to a paradoxical response. She had been suffering for 1 month from low back pain, due to tuberculous spondylitis. Her low back pain improved after antituberculous therapy. The low back pain, however, reappeared 2 months after treatment, accompanied by newly developed lower extremity weakness. Imaging studies showed an increased extent of her previous lesions. Consequently, the patient underwent a vertebral corpectomy with interbody fusion of the thoracolumbar spine. Histopathological examination showed chronic inflamed granulation tissue with no microorganisms. Although the antituberculous medication was not changed, the patient\'s symptoms and signs, including the paralysis, resolved after surgery.