Case Problem – A 55-year-old male with fatigue, weight reduction and pulmonary nodules – NEJM

presentation of the case

dr Jarone Lee: A 55-year-old man was admitted to this hospital 7 months after kidney transplantation because of fatigue, weight loss and new pulmonary nodules.

The patient was in his usual state of health up to 1 week before this admission, when severe fatigue and general weakness set in. He had lost 10 pounds in the past month after eating healthier; however, he had also noticed abdominal discomfort and loss of appetite.

In the following week the patient could eat and drink very little and lost another 4.5 kg. The fatigue and weakness worsened and he stayed in bed most of the time. He had several episodes of lightheadedness, unsteady gait, and falling while going to the bathroom. There were new odynophagia, dysphagia and nausea.

On the day of admission, the patient was evaluated prior to a scheduled belatacept infusion at the transplant nephrology clinic at this hospital. Temperature was 37.3 °C, blood pressure 70/50 mm Hg, heart rate 98 beats per minute, respiratory rate 35 breaths per minute, and oxygen saturation 96% while breathing ambient air. He seemed cachectic and lethargic. He was transported by ambulance from the clinic to the emergency department of this hospital.

In the emergency room, the patient reported being unwell and feeling like he had no energy or strength. The drowsiness and unsteady gait persisted. A review of the systems was notable for shortness of breath, dark urine and persistent anorexia, nausea, odynophagia, dysphagia and abdominal discomfort. He reported no chills, night sweats, cough, chest pain, vomiting, hematochezia, melena, or dysuria.

The patient had a history of sarcoidosis. Nine years prior to this recording, nephrocalcinosis caused end-stage kidney disease. Hemodialysis was initiated and continued on this treatment until a deceased donor kidney transplant was performed 7 months prior to this admission. Routine serological tests performed prior to transplantation were positive for Epstein-Barr virus (EBV) IgG and cytomegalovirus (CMV) IgG. An interferon-γ release assay for Mycobacterium tuberculosis was negative. The donor’s serological tests were also positive for EBV-IgG but negative for CMV-IgG. Immunosuppressive induction therapy with antithymocyte globulin was initiated; Maintenance therapy included prednisone, mycophenolate mofetil, and tacrolimus.

Six months prior to current enrollment, pathologic examination of a biopsy specimen from the transplanted kidney revealed donor vascular disease and acute tubular injury, but no evidence of T-cell-mediated or antibody-mediated rejection. Tacrolimus treatment was discontinued and belatacept was started; Prednisone and mycophenolate mofetil therapy was continued.

One month prior to the current enrollment, pathologic examination of another biopsy specimen from the transplanted kidney showed focal infiltrates that were vaguely granulomatous and associated with ruptured tubules and interstitial Tamm-Horsfall protein (also known as uromodulin). There was no evidence of allograft rejection.

Table 1. Laboratory data. Table 1 Figure 1. Breast imaging studies obtained at admission. illustration 1 Figure 1. Breast imaging studies obtained at admission. A frontal x-ray (panel A) shows multiple tiny pulmonary nodules (arrows) diffusely scattered over both lungs in a miliary pattern. Coronal (Panel B) and axial (Panel C) images from a CT on lung windows show numerous small bilateral nodules (yellow arrows) that are new compared to the images obtained 6 months previously. The distribution of the nodules is random, a feature suggestive of a hematogenous origin. There is a small right pleural effusion (panel C, blue arrow). A coronal CT image obtained with soft-tissue windows (panel D) shows enlarged bilateral hilar and subcarinal lymph nodes that are partially calcified (arrows). These findings are consistent with the known history of chronic sarcoidosis. Figure 2. CT of the abdomen and spleen. figure 2 Figure 2. CT of the abdomen and spleen. Shown are coronal images of the abdomen obtained with soft tissue windows from CT performed without the administration of intravenous contrast material 6 months prior to admission (ie, baseline) (panel A) and at admission (panel B). Splenomegaly has developed, with the spleen measuring 16 cm on admission. A small volume of new perihepatic ascites is also present (arrow).

Laboratory tests two weeks before the current admission showed a blood creatinine level of 2.31 mg per deciliter (204.2 μmol per liter; reference range 0.60 to 1.50 mg per deciliter). [53.0 to 132.6 μmol per liter]); Routine laboratory tests had revealed similar creatinine levels over the previous 6 months. Other laboratory test results are shown in FIG Table 1.

The patient also had a history of hypertension, hyperlipidemia, and gout. Current medications included aspirin, atorvastatin, labetalol, nifedipine, trimethoprim-sulfamethoxazole, valganciclovir, prednisone, mycophenolate mofetil, and belatacept. There were no known drug allergies. The patient lived with his mother in an urban area of ​​New England and had never traveled outside of the area. He worked as an administrator and had never been homeless or incarcerated. He had no sexual partners and did not smoke tobacco, use illegal drugs or drink alcohol.

On the day of examination in the emergency department, temperature was 36.7 °C, blood pressure was 80/50 mm Hg, heart rate was 100 beats per minute, respiratory rate was 24 breaths per minute, and oxygen saturation was 92% during which the patient was breathing ambient air. The body mass index (the weight in kilograms divided by the square of the height in meters) was 20.5. The patient was lethargic and spoke in sentences of three or four words. The mucous membranes were dry and the throat could not be evaluated because of nausea. There was no cervical lymphadenopathy. Auscultation of the lungs showed a diffuse inspiratory crackle. Neurological examination was limited but was notable for 4/5 motor strength in arms and legs.

The blood level of creatinine was 5.05 mg per deciliter (446.4 μmol per liter), the calcium level was 13.1 mg per deciliter (3.3 mmol per liter; reference range 8.5 to 10.5 mg per deciliter). [2.1 to 2.6 mmol per liter]), the lactic acid content 4.4 mmol per liter (39.6 mg per deciliter; reference range 0.5 to 2.0 mmol per liter [4.5 to 18.0 mg per deciliter]) and the hemoglobin value 6.6 g per deciliter (reference range 13.5 to 17.5). Blood cultures were obtained. Other laboratory test results are shown in FIG Table 1.

dr Mark C Murphy: Computed tomography (CT) of the chest, abdomen and pelvis was performed without the administration of intravenous contrast medium. CT of the chest (illustration 1) showed innumerable bilateral miliary lung nodules that were new compared to a CT scan obtained 6 months earlier. The nodules were present in a random distribution suggesting a hematogenous origin. Traces of bilateral pleural effusions were present, as were calcified mediastinal and bilateral hilar lymphadenopathy; lymphadenopathy appeared unchanged from previous imaging. CT of the spleen (figure 2) showed a new splenomegaly. There was a new slight dilatation of the renal collecting system of the transplanted kidney in the right lower quadrant of the abdomen.

dr Lee: While the patient was being examined in the emergency room, the temperature rose to 39.6°C. Intravenous fluids and an intravenous infusion of phenylephrine were administered. Empirical treatment with vancomycin, cefepime, metronidazole, levofloxacin, doxycycline, and micafungin was started; Trimethoprim-sulfamethoxazole and valganciclovir were continued. Treatment with prednisone and mycophenolate mofetil was discontinued and hydrocortisone therapy started. The patient was admitted to the intensive care unit.

Within 24 hours of admission, oxygen saturation had dropped to 84% while the patient was breathing ambient air; supplemental oxygen was administered through a nasal cannula at a rate of 2 liters per minute and oxygen saturation increased to 94%. Continuous intravenous infusion of phenylephrine was continued and norepinephrine was added to maintain mean arterial pressure above 65 mm Hg. Two units of packed red blood cells were transfused. Creatinine levels fell to 3.82 mg per deciliter (337.7 μmol per liter), lactic acid levels to 1.6 mmol per liter (14.4 mg per deciliter) and calcium levels to 8.9 mg per deciliter (2.2 mmol per liter). Treatment with levofloxacin and micafungin has been discontinued; Isavuconazole was started.

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