We present the case of a 46-year-old woman with unremarkable medical history, initially visited her primary care physician multiple times complaining of a sore throat. At the initial presentation, under suspicion of viral pharyngitis, only symptomatic treatment was prescribed, and the patient was sent home. After one week, there was no significant improvement, prompting the patient to revisit her primary care physician. At this point there was a sudden deterioration in her general condition, characterized by sore throat, difficulty swallowing, chills, dyspnea, fever, and marked weakness. Consequently, the patient was presented to the emergency department of a smaller hospital in her hometown. The transfer report indicated that, at this time, the patient was already in a state of sepsis, characterized by hepatopathy (serum bilirubin = 1.4 mg/dl), thrombocytopenia (platelets = 30,000/µl), mild oxygenation impairment with a requirement of 4 L of oxygen, and an increased respiratory rate (> 22/min) as well as a high heart rate (120/min) and low blood pressure (100/60 mmHg). Based on the clinical picture, septic shock was assumed, and broad-spectrum therapy with piperacillin/tazobactam was immediately initiated, with the patient admitted to the intensive care unit. In the context of environmental diagnostics, a chest X-ray revealed an approximately 3 × 3 × 2 cm round density in the right upper lung field. Her condition then quickly stabilized. Due to the additional suspicion of tuberculosis at the smaller hospital, she was transferred to our clinic, a university hospital and a tertiary care facility, after a three-day stay. So, approximately 2 weeks passed from the onset of symptoms to admission to our clinic. On the day of admission an additional computed tomography (CT) imaging showed multiple pulmonary nodules of varying morphology. Overall, multiple bilateral round lesions were visible, especially subpleural. Some were described as cavitary lesions [Fig. 1] and others displaying a reversed-halo sign [Fig. 2] [8]. One lesion was described as partially beginning to liquefy, some with bronchopneumogram, along with probable atelectatic consolidations in the lower lobes dorsobasal. Additionally, there were accompanying pleural effusions on both sides and increased to borderline-sized mediastinal lymph nodes. Although a diverse range of pulmonary masses is evident, the report also shows characteristic signs of septic emboli [9]. Serology revealed elevated levels of total immunoglobulin E and anti-aspergillus immunoglobulin G with non-detectable galactomannan and beta-glucan. Since we had no evidence of an atypical bacterial pathogen spectrum based on the anamnesis and imaging, we de-escalated the therapy to ampicillin/sulbactam in line with antibiotic stewardship principles, under which there was further clinical and laboratory improvement. Other possible and important differential diagnoses were ruled out. We first conducted an extensive serological testing to rule out vasculitis or autoimmune disease. Specifically, this included: ANA-, ANCA-IFT, MPO- and PR3-immunoassay, C3 and C4 component, Anti-ds-DNA-, Anti-CENP-B-, Anti-SCL70, Anti-Jo1-, Anti-Sm-D-, Anti-SS-A(Ro60)-, Anti-SSA52-, Anti-SS-B-immunoassay. The HIV test was negative. Furthermore, ferritin levels were measured, a quantitative determination of immunoglobulins with an IgG subclass analysis was performed, as well as serum protein electrophoresis. Apart from the elevated IgE levels, no abnormal values were detected. The diagnosis of sarcoidosis is complex. A bronchoscopy performed by pulmonologists revealed macroscopically normal mucosa. The differential cytology of a bronchoalveolar lavage from the middle lobe showed an inflammatory profile (62% macrophages, 32% lymphocytes, 5.7% granulocytes). A transbronchial biopsy from segment S1/2 demonstrated an active inflammatory picture in the cytological analysis without atypia, tumor cells, granulomas, or signs of vasculitis. To definitively rule out sarcoidosis or malignancy, an Endobronchial ultrasound (EBUS)-guided lymph node biopsy would have been additionally required. However, considering the overall findings, sarcoidosis seemed unlikely, especially since there was radiological and clinical improvement with the initiated therapy. To rule out tuberculosis, an interferon-gamma release assay was conducted, which returned negative. Additionally, bronchoalveolar lavage and transbronchial biopsy were examined microscopically for acid-fast bacilli and tested via PCR for mycobacteria, each yielding normal findings.

CT scan of the chest at level of aortic arch (day of admission): cavitary lesion in the left upper lobe of the lung

CT scan of the chest at lower thoracic level (day of admission): ground-glass appearance with surrounding consolidation (reversed halo-sign) in the right upper lobe of the lung

In summary, a diagnosis of chronic pulmonary aspergillosis was suspected. During hospitalization, the sore throat worsened and spread to the area of the left lateral neck. Ultrasound examination revealed a complete thrombosis of the left internal jugular vein [Fig. 3], which was confirmed by CT angiography. Considering the initial highly septic condition and the symptom of a sore throat, Lemierre Syndrome was suspected. Imaging showed pulmonary lesions of diverse morphology, including round lesions partially beginning to liquefy and larger lesions typical for chronic pulmonary aspergillosis. Although the case described aligns with the findings indicative of Lemierre syndrome, pathogen identification was unfortunately unsuccessful, particularly in the blood cultures obtained. Since the patient was promptly treated with a broad-spectrum antibiotic at the smaller hospital upon the presentation of sepsis, no pathogen could be identified there or in our hospital. We do not know when and how many blood cultures were taken at the transferring hospital; however, upon admission to our facility, two sets were taken, and two additional sets were obtained over the first week, all of which showed no pathogen growth. The patient received guideline-recommended sepsis therapy and antifungal therapy using voriconazole with therapeutic drug monitoring for three months [7]. Voriconazole was administered at a dose of 200 mg twice daily. Target levels were initially monitored weekly and then every two weeks, remaining within the range of 1–5 mg/l. After a total hospital stay of two weeks, including the first three days in intensive care at the smaller hospital, the patient was discharged in a stabilized general condition. A follow-up CT after three months showed regression of the pulmonary nodules. No pulmonary foci were detectable after three months of therapy [Fig. 4]. Particularly no repeat Aspergillus IgG testing, was conducted after three months. Given the remarkable clinical and imaging response, serological monitoring was omitted, although it should have been included for comprehensive follow-up.

Sonography of the left neck (6 days after admission to our hospital): complete thrombosis of the internal jugular vein

CT scan of the chest after three months of antifungal therapy (after 3 months of antifungal therapy, administered on an outpatient basis)

The finding of the thrombosis of the internal jugular vein was immediately reviewed with our angiologist colleagues, who recommended therapeutic anticoagulation. This was initially carried out with enoxaparin at a therapeutic dose (5,000 IU twice daily) for a total of eight days until discharge. With normal renal function, it was then switched to apixaban at 5 mg twice daily. The first out specialist angiological follow-up took place 3.5 months after discharge, revealing via sonography an indistinct left internal jugular vein, likely rarefied by the thrombus. Another CT scan was conducted six months later, confirming a completely obliterated left internal jugular vein, which appeared to be collateralized via vertebral vein branches. At this point, D-dimers were undetectable in lab results (< 0.19 mg/l), leading to the discontinuation of oral anticoagulation.