Cases from Oregon Health & Science University

Emphysematous pyelonephritis, copper deficiency, and more.


Case 1: Emphysematous pyelonephritis in polycystic kidney disease

By Morris M. Kim, MD, ACP Resident/Fellow Member; Peter S. Fong, MD, ACP Resident/Fellow Member; and Zachary G. Jacobs, MD

The patient

Figure 1 CT showing cysts and polycystic kidneys with gas within the left kidney white arrows
Figure 1. CT showing cysts and polycystic kidneys with gas within the left kidney (white arrows).

A 57-year-old man with no known comorbidities presented to the ED with one week of malaise, chills, and left-sided abdominal fullness. He had no dysuria or flank pain. Physical exam was notable for a heart rate of 105 beats/min, blood pressure of 137/72 mm Hg, respiratory rate of 23 breaths/min, and a grossly distended abdomen. Labs were notable for white blood cell count of 28,700 cells/mm3 (reference range, 4,000 to 11,000 cells/mm3), blood urea nitrogen level of 228 mg/dL (reference range, 6 to 20 mg/dL), creatinine level of 18 mg/dL (reference range, 0.6 to 1.2 mg/dL), serum bicarbonate level of 5 mmol/L (reference range, 22 to 32 mmol/L), and pH of 7.01 (reference range, 7.32 to 7.42). His baseline renal function was unknown; despite an abnormal creatinine level of 3.18 mg/dL (reference range, 0.6 to 1.3 mg/dL) recorded two years prior, he had been lost to follow-up. A urine culture grew Klebsiella pneumoniae and Escherichia coli, and blood cultures grew Klebsiella pneumoniae. A CT of the abdomen showed numerous hepatic cysts and large polycystic kidneys with intraparenchymal gas within the left kidney (Figure 1).

He was treated with IV piperacillin/tazobactam and started on urgent hemodialysis on hospital day 1. On hospital day 3, he underwent percutaneous catheter drainage, which was complicated by septic shock and acute hypoxic respiratory failure, briefly requiring intubation and vasopressors immediately following the procedure. After extubation and hemodynamic stabilization, he was transferred to a tertiary hospital to be considered for an emergency nephrectomy. The inpatient urology service instead recommended conservative management with antibiotics and ongoing percutaneous drainage. He was discharged after clinical improvement, with follow-up imaging revealing improvement of emphysematous changes. He is currently undergoing evaluation for renal transplantation.

The diagnosis

The diagnosis is autosomal-dominant polycystic kidney disease complicated by emphysematous pyelonephritis (EPN), a necrotizing gas-forming infection within the renal parenchyma and its surrounding tissue. Major risk factors for EPN include diabetes, polycystic kidneys, end-stage renal disease, immunosuppression, and urinary tract obstruction. It is more common among women and older adults. Diagnosis is made with radiographic findings of gas within the renal parenchyma in the setting of an acute urinary tract infection. Escherichia coli and Klebsiella pneumoniae are the two most commonly isolated pathogens. Empiric antibiotic selection depends on severity of illness, host factors, and risk for resistant organisms but should target common urinary pathogens and be subsequently tailored based on culture data.

The management of EPN historically involved nephrectomy or open drainage in addition to systemic antibiotics. More recently, conservative management with antibiotics plus percutaneous catheter drainage has become the initial treatment of choice. Conservative management can decrease morbidity by potentially preserving residual kidney function compared to an emergency nephrectomy. More important, it has been associated with decreased mortality compared to emergency nephrectomy or antibiotics alone. However, the existing literature on management of EPN is limited to meta-analyses of retrospective studies and case reports/case series of small populations, so nephrectomy may still occasionally be used in high-risk patients and management decisions should be based on individualized risk-benefit discussions. Prognostic factors reported to be associated with poor outcomes include thrombocytopenia, hypoalbuminemia, azotemia, need for urgent dialysis, shock at initial presentation (systolic blood pressure <90 mm Hg), polymicrobial infection, and extension of infection into the perinephric space. In a 2014 retrospective study of 44 patients diagnosed with EPN, published in BMC Infectious Diseases, multivariate analysis showed that only hypoalbuminemia was found to be an independent risk factor for failure of conservative treatment. Mortality from EPN is commonly related to complications of sepsis.

Pearls

  • Prompt diagnosis of EPN through cross-sectional imaging revealing gas within the renal parenchyma is crucial to enable timely treatment.
  • Treatment of EPN with early antibiotics and percutaneous drainage can minimize the need for more invasive procedures and improve mortality risk.

Case 2: Adverse local tissue reaction to metal hip prosthesis

By Brian McGarry, MD, ACP Resident/Fellow Member; Sajan Gill, MD; David Sauer, MD; Patricia Fenderson, MD, PhD; and Stephanie Halvorson, MD, FACP

The patient

Figure 2 CT showing fluid collection in the right iliacus muscle red arrow and hyperattenuating metal implant with scatter artifact blue arrow
Figure 2. CT showing fluid collection in the right iliacus muscle (red arrow) and hyperattenuating metal implant with scatter artifact (blue arrow).

A 74-year-old man who had right metal-on-metal (MoM) total hip arthroplasty performed 10 years prior presented with one day of severe right hip pain, fevers, and rigors. Physical exam was significant for fever to 101.8 °F (38.7 °C) and pain on right hip flexion with reduced range of motion. Labs revealed leukocytosis with bandemia and elevated inflammatory markers. A CT of the abdomen and pelvis revealed a large intramuscular fluid collection in the right iliacus muscle (Figure 2).

Vancomycin and piperacillin/tazobactam were initiated out of concern for sepsis due to intramuscular abscess and prosthetic joint infection. The patient underwent aspiration of the iliacus fluid and right hip synovial fluid, which appeared purulent. Both samples were gram stain- and culture-negative, though antibiotics had been initiated prior to sampling. A manual cell count could not be obtained as the samples were too viscous for analysis.

Figure 3 Synovium biopsy showing macrophages with granular material indicative of metallosis red arrow and many neutrophils blue arrow
Figure 3. Synovium biopsy showing macrophages with granular material indicative of metallosis (red arrow) and many neutrophils (blue arrow).

Serum metal studies showed a cobalt level of 6.6 μg/L (reference range ≤3.9 μg/L) and chromium level of 4.3 μg/L (reference range ≤5 μg/L). Operative irrigation with prosthetic revision was performed, revealing thick, white-brown fluid. Surgical pathology on synovium biopsies revealed prosthesis-related metallosis and neutrophils suggestive of acute inflammation (Figure 3).

The diagnosis

The diagnosis is adverse local tissue reaction (ALTR) with superimposed prosthetic joint infection. ALTR refers to local cytotoxicity and hypersensitivity reaction to metal implant debris leading to soft-tissue damage and cystic mass formation (pseudotumor). The cumulative incidence of prosthetic joint infection is between 1% and 2% at 10 years, with most cases occurring within two years of implantation. ALTR is estimated to occur in 30% to 60% of patients with MoM hip implants, though the majority are asymptomatic. Time to ALTR onset varies with composition, prosthesis model, and patient susceptibility to debris. Time from implantation is a significant risk factor for development of ALTR. MoM hip prostheses were widely popular until 2010 when emerging data suggested higher rates of failure and associated complications. It is estimated that more than 1 million MoM joint implantations were performed worldwide between 1996 and 2015.

There are currently no formal guidelines for serum ion level monitoring, but a chromium or cobalt level greater than 7 parts per billion (ppb) should prompt follow-up imaging. A level greater than 20 ppb (especially cobalt) is concerning for toxicity; although rare, case reports have described neurologic, renal, and cardiac effects. Serum ion levels do not have a dose-response relationship with degree of local tissue destruction. Levels should be obtained in patients with a symptomatic MoM joint but should not be used alone to guide need for revision surgery.

It can be difficult to distinguish ALTR from prosthetic joint infection in a patient with pain at a MoM hip prosthesis. Both conditions have similar clinical presentations, and serum inflammatory markers are typically elevated. Making the distinction between ALTR and prosthetic joint infection often requires synovial fluid aspiration, ideally prior to antibiotics. Manual cell count, differential, and culture are the most sensitive and specific studies to distinguish between the two conditions. A higher neutrophil count is suggestive of prosthetic joint infection, and aseptic fluid cultures rule it out. Most patients with ALTR require revision arthroplasty, while those with prosthetic joint infection may require debridement and revision, as well as prolonged courses of antibiotics.

Pearls

  • ALTR and prosthetic joint infection can present similarly and may be difficult to differentiate; greater time from MoM joint implantation and elevated serum ion levels increase suspicion for ALTR.
  • Synovial fluid manual cell count, differential, and culture are key to discerning between ALTR and prosthetic joint infection.

Case 3: Symptomatic copper deficiency secondary to enteral nutrition

By Raj Nagappan, MD, ACP Resident/Fellow Member; Jonathan Taylor, MD, ACP Resident/Fellow Member; and Peter Sullivan, MD, FACP

The patient

A 75-year-old man with a history of atrial fibrillation, duodenal ulcers, and gastric outlet obstruction requiring artificial feeding via jejunostomy tube was brought to the hospital from his nursing facility with fever and productive cough. Vitals on admission were notable for hypoxia requiring 2 L of supplemental oxygen and were otherwise normal. On initial physical examination, the patient was found to be rigid in a cogwheel pattern with bilateral upper-extremity resting tremors. Laboratory studies were notable for a new bicytopenia: leukopenia with a white blood cell count of 2,900 cells/mm3 (reference range, 3,500 to 10,800 cells/mm3) and anemia with a hemoglobin level of 8 g/dL (reference range, 13.5 to 17.5 g/dL). Chest X-ray showed a left lower lobe infiltrate, and antibiotics were initiated for pneumonia. Further history revealed the patient had been experiencing progressive personality changes over several months and had lost the ability to walk.

Given the triad of anemia, leukopenia, and neurologic deficits in the setting of exclusive jejunostomy tube feeding, there was a concern for a malabsorptive process contributing to this presentation. A copper level returned at 13 μg/dL (reference range, 70 to 140 μg/dL). The ceruloplasmin level was 18 mg/dL (reference range, 17 to 54 mg/dL), and other vitamin and micronutrient levels were unremarkable. The patient completed an antibiotic course for pneumonia, began parenteral copper therapy, and was ultimately discharged back to his nursing facility.

The diagnosis

The diagnosis is copper deficiency in the setting of jejunal enteral nutrition. Copper is an essential component of metabolic cellular transporters involved in hemoglobin synthesis, iron metabolism, cellular respiration, and neurotransmission. Recommendations call for adults to consume 1 to 3 mg of dietary copper per day, and early recognition of deficiency is crucial for preventing complications. Neurologic symptoms include myelopathies, peripheral neuropathy, gait spasticity, and sensory ataxia. Hematologically, a classic bicytopenia of anemia and leukopenia has been well described. Common causes of copper deficiency include gastric bypass surgery, conditions causing malabsorption, and high zinc intake, with symptom onset reported as early as six months following the inciting etiology. Copper is primarily absorbed in the stomach and proximal duodenum, so patients receiving nutrition bypassing this region of the gut are at increased risk. Diagnosis can be made by measuring serum copper and ceruloplasmin levels, or from a 24-hour urine copper level. Hematologic manifestations respond promptly to copper replacement; however, neurologic symptoms are generally irreversible, making early diagnosis essential for good outcomes. Bariatric surgery guidelines recommend routine copper level surveillance as a component of micronutrient screening to ensure optimal postbypass nutritional support. Once copper supplementation is initiated, levels should be monitored every few months to ensure appropriate dosing.

Pearls

  • Copper is primarily absorbed in the stomach and proximal duodenum, and patients receiving nutrition in a way that bypasses this region are at an increased risk for copper deficiency.
  • Early diagnosis of copper deficiency is essential because hematologic manifestations respond promptly to copper replacement, but neurologic symptoms are generally irreversible.

Case 4: Mycobacterium chelonae infection misdiagnosed as erythema nodosum

By Lexy Fancher-Dominguez, MD, ACP Resident/Fellow Member; Stephen Lockwood, ACP Medical Student Member; Simone E. Dekker, MD, PhD, ACP Resident/Fellow Member; and Sima Desai, MD, FACP

The patient

A 68-year-old man with a history of ventricular fibrillation arrest resulting in ICD placement and presumed isolated cardiac sarcoid who was on chronic immunosuppression with adalimumab and prednisone presented with COVID-19 infection. In addition to respiratory symptoms, he reported a two-month history of multiple erythematous nodules on his right lower leg with edema. This had been diagnosed in clinic as erythema nodosum and was being treated with dapsone. He did not report any environmental or animal exposures.

Figure 4 Right anteriorslashmedial shin showing red purple-brown indurated plaques
Figure 4. Right anterior/medial shin showing red, purple-brown, indurated plaques.
Figure 5 Photomicrograph details suppurative and granulomatous dermatitis with central caseation and gram-positive bacteria
Figure 5. Photomicrograph details suppurative and granulomatous dermatitis with central caseation and gram-positive bacteria.
Figure 6 Photomicrograph details acid-fast bacillus-positive filamentous bacteria
Figure 6. Photomicrograph details acid-fast bacillus-positive filamentous bacteria.

On examination, he had indurated red, purple-brown nodular plaques and surrounding edema on his right medial knee and shin (Figure 4). The patient was continued on his home prednisone, adalimumab was held, and he was not treated with any additional steroids for COVID-19 infection. Dapsone was discontinued during his admission due to macrocytic anemia concerning for hemolysis from possible G6PD deficiency. He had subsequent worsening of existing lesions and new lesions developing on his right upper thigh. Given the atypical nature of his skin findings and progression, skin biopsy was performed. Pathology demonstrated suppurative and granulomatous dermatitis with necrosis and gram-positive/acid fast-positive filamentous bacteria (Figure 5, Figure 6). Cultures and probe assay identified Mycobacterium chelonae.

The diagnosis

The diagnosis is skin and soft-tissue infection (SSTI) with M. chelonae, a rapidly growing mycobacterium (RGM). Other RGM species include M. fortuitum and M. abscessus, of which M. fortuitum is the most common. Classically, erythema nodosum presents with bilateral lower-extremity lesions rather than the unilateral lesions with thigh involvement as seen in this patient. Pulmonary and hematological manifestations may also occur. M. chelonae infections are more common in patients immunosuppressed with prednisone or T-cell-directed agents, such as adalimumab, both of which this patient was taking. Infectious sources include botulinum toxin injections, liposuction, tattooing, and contaminated foot baths in nail salons. Clinical presentation is variable and classically includes tender, erythematous, draining nodules, though the condition may present as chronic, nonhealing cellulitis or skin ulcers with hyperpigmentation. This polymorphic presentation makes it challenging to distinguish between M. chelonae infection and other cutaneous disorders. The incidence of nontuberculous mycobacterial infections is increasing, but disease reporting is not mandatory and the burden of disease from individual species is unknown.

This case demonstrates that unusual skin lesions or lesions that do not respond to typical therapy should be biopsied and sent for mycobacterial culture. Delayed diagnosis increases risks of medication side effects and the potential for worsening of clinical disease. It is essential to differentiate between M. chelonae and erythema nodosum but also other similar-appearing skin infections, such as blastomycosis, actinomycosis, and nocardiosis, as treatments may be significantly different. Treatment of limited M. chelonae SSTI includes two agents for a minimum of four months, such as a macrolide plus a fluoroquinolone, a tetracycline, or trimethoprim-sulfamethoxazole. For extradermatologic infections or extensive skin involvement, treatment should initially be parenteral with two or three agents to which the organism is susceptible, followed by oral treatment for six to 12 months.

Pearls

  • Nontuberculous mycobacterial infections such as M. chelonae are increasing in incidence, and they often have variable presentation that leads to misdiagnosis.
  • Treatment of M. chelonae SSTIs includes a prolonged course of multiple antibiotics to which the organism is susceptible, and duration depends on the severity of the infection.

Case 5: Rapidly progressive purulent pericarditis

By Ryan M. Kane, MD, MPH, ACP Resident/Fellow Member; Caroline Doan, DO, ACP Resident/Fellow Member; and Kevin Piro, MD, ACP Member

The patient

Figure 7 Echocardiogram showing diffuse concave ST elevations and PR depressions
Figure 7. Echocardiogram showing diffuse concave ST elevations and PR depressions.

A 23-year-old man with a medical history significant for multiple SSTIs in the context of IV heroin and inhaled methamphetamine use presented with acute onset of severe, positional chest pain that improved upon sitting upright. He was afebrile, normotensive, and tachycardic. Initial evaluation showed sinus tachycardia with diffuse ST elevation on electrocardiogram (Figure 7) and a small circumferential pericardial effusion without evidence of tamponade on transthoracic echocardiogram. Colchicine and ibuprofen were started with a plan for outpatient follow-up.

Figure 8 Point-of-care ultrasound showing large circumferential pericardial effusion PE in the parasternal long axis view arrows with a view of the right ventricle RV left ventricle LV and
Figure 8. Point-of-care ultrasound showing large circumferential pericardial effusion (PE) in the parasternal long axis view (arrows), with a view of the right ventricle (RV), left ventricle (LV), and left ventricular outflow tract (LVOT).

However, less than 24 hours later, he was admitted with concern for sepsis due to persistent chest pain, fever to 100.4 °F (38 °C), heart rate of 121 beats/min, respiration rate of 28 breaths/min, and rapidly rising neutrophilic leukocytosis (from 12,930 cells/mm3 to 16,650 cells/mm3; reference range, 3,500 to 10,800 cells/mm3) and lactate levels (from 0.9 mmol/L to 1.9 mmol/L; venous reference range, 0.5 to 2.2 mmol/L). Upon admission he was diaphoretic and writhing from chest pain and had mild jugular venous distension, distant heart sounds without friction rub, and numerous skin excoriations without evidence of an acute cellulitis or abscess. Blood cultures were sent, and broad-spectrum antibiotics were initiated. Two hours later, he became hypotensive with minimal fluid responsiveness despite 3 L of lactated Ringer's solution over 24 hours (blood pressure changed from 70/50 mm Hg to 98/74 mm Hg). His pulsus paradoxus exam was normal at 7 to 8 mm Hg (reference range ≤10 mm Hg), but a cardiac point-of-care ultrasound (POCUS) displayed a moderate fibrinous pericardial effusion notably larger than on the initial echocardiogram less than 24 hours prior (Figure 8). Out of concern for impending tamponade, the patient was transferred to the cardiovascular ICU and several hours later received a pericardiocentesis with drain placement that yielded 330 mL of cloudy fluid. Fluid cultures were positive for methicillin-resistant Staphylococcus aureus (MRSA).

The diagnosis

The diagnosis is MRSA purulent pericarditis. MRSA purulent pericarditis is a rare phenomenon with only case reports available. They report associations with immunodeficiency, comorbid abscesses, historical MRSA infections, and recent surgery or radiation involving the pericardium. IV substance use disorders are likely an underreported association, due to stigma and recent increases in MRSA infections and IV substance use. Of note, acute pericarditis is diagnosed in about 0.1% of hospitalized patients with only 1% to 2% of all pericardial effusions evolving from a bacterial source (most frequently from Streptococci, Staphylococci, Haemophilus, and Mycobacterium tuberculosis). In particular, MRSA pericarditis frequently progresses to cardiac tamponade (44% to 72% of patients), has a high mortality rate (up to 60%), has the potential for recrudescence, and often requires definitive source control (pericardiocentesis, typically with pericardial drain placement, saline or thrombolytic washout, and/or pericardial window).

Pulsus paradoxus has a sensitivity of 82% and can increase the clinical likelihood of cardiac tamponade, but its absence does not necessarily rule out the diagnosis. Similarly, transthoracic echocardiography is highly accurate for tamponade, but it provides only a snapshot in time and can miss rapidly evolving cases. POCUS can be an essential diagnostic tool to effectively identify patients at risk for tamponade, as it has a sensitivity of 96% and specificity of 98% for detection of a pericardial effusion. In this case, serial evaluation of an effusion in an undifferentiated hypotensive patient identified rapidly progressive pericardial effusion and evolving tamponade. The rapidly progressive nature of this patient's effusion along with its early detection and hypotension likely affected the initial pulsus paradoxus exam. As hemodynamic effects of tamponade vary on a continuum, a high index of clinical suspicion along with the use of multiple tools for bedside evaluation are key to diagnosis.

Pearls

  • It is important to maintain a high index of clinical suspicion for MRSA pericarditis in patients with risk factors (e.g., substance use, history of MRSA infection, immunodeficiency, comorbid abscesses, and recent regional surgeries/radiation).
  • Clinicians should use multiple diagnostic tools to critically assess patients with pericarditis when concerned for tamponade, including point-of-care ultrasound and the pulsus paradoxus exam.

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