A rare case of community-acquired necrotizing pneumonia in a patient treated with adalimumab therapy

Abstract

Background

Necrotizing pneumonia is a life-threatening complication of community-acquired pneumonia managed in an intensive care setting with a multitude of diagnostic modalities and numerous therapeutic interventions. Pseudomonas aeruginosa remains an extremely uncommon organism known to cause necrotizing pneumonia, and of the cases reported, are almost entirely found in immunocompromised hosts.

Case details

Here, we report a case of Pseudomonas aeruginosa community-acquired necrotizing pneumonia in a host receiving adalimumab therapy that ultimately was not able to be healed despite targeted antibiotics.

Conclusion

Adalimumab is known to immunosuppress patients and increase risk of tuberculosis and fungal disease, but have unclear associations with other infections. This case exemplifies a rare encounter of Pseudomonas aeruginosa necrotizing pneumonia in a patient on adalimumab therapy contracted through the community. Treatment of necrotizing pneumonia in patients on adalimumab therapy does not differ significantly from other cases of non-adalimumab associated necrotizing pneumonia.

Background

Necrotizing pneumonia is a detrimental complication of community-acquired or hospital-acquired pneumonia, characterized by the destruction, liquefaction, and cavitation of lung parenchyma, typically induced by a bacterial microbe [1]. Initially documented in the 1940 s, necrotizing pneumonia has been a rare diagnosis associated with mortality rates of up to 45% in adults and children [2]. Very few studies have assessed the number of patients with necrotizing pneumonia; however, some studies have indicated an underdiagnosis among community-acquired pneumonia cases. A retrospective study noted an incidence rate of approximately 10%, which may represent a lack of diagnostic understanding [3]. In this section, we describe the microbiological etiologies, pathogenesis, clinical presentation, diagnostic approach, medical and surgical treatment, prognosis, and, as it relates to this case, the risks associated with adalimumab therapy.

Microbiological etiologies of necrotizing pneumonia

Generally, most pathogens capable of inducing lobar pneumonias are frequently associated with necrotizing pneumonia. Clinically, necrotizing pneumonia in adults is usually community-acquired, with the most common infectious organisms being Streptococcus pneumoniae, Staphylococcus aureus, and Klebsiella pneumoniae [1].

Pseudomonas aeruginosa is a very unusual causative organism of both community-acquired pneumonia and necrotizing pneumonia. Typically, patients presenting with Pseudomonas aeruginosa pneumonia are hospitalized, ventilated, or have chronic respiratory colonization with Pseudomonas [4]. Only a handful of cases exist in the current literature illustrating the association of Pseudomonas aeruginosa with community-acquired necrotizing pneumonia. A Japanese case report published in 2012 describes a case of community-acquired Pseudomonas aeruginosa necrotizing pneumonia in a young male with no discernible evidence of immunocompromise. This patient’s workup was negative for HIV and human T-lymphotropic virus type 1 (HTLV-1), and had unremarkable serum immunoglobulins and complement levels. This ultimately raises questions about how Pseudomonas was contracted and how the infection quickly manifested. This patient required admission to a medical intensive care unit (MICU) and was ultimately treated with several weeks of anti-pseudomonal antibiotics, resulting in clinical improvement [5].

Pathogenesis

The pathogenesis of Pseudomonas aeruginosa pneumonia is complex, resulting from the synergistic action of bacterial cytotoxins and dysregulated host inflammatory responses, which yield extensive pulmonary necrosis and hemorrhage.

Pseudomonas aeruginosa pneumonia typically first occurs when the human airway epithelium is breached, allowing access to the basolateral membranes. The airway epithelium is the primary defense against most pathogens, serving as a physical barrier. The role of biofilm formation by Pseudomonas and impaired mucociliary clearance, frequently observed in many predisposing respiratory conditions (e.g., cystic fibrosis), also plays a crucial role in Pseudomonas aeruginosa pulmonary infections [7]. Breaches to expose the basolateral surface of epithelium usually occur through either pre-disposed, injured epithelium [7], cells that are currently in a remodeling/repair stage and are susceptible to infiltrative pathogens [8], or through a non-pathological mechanism due to normal cell renewal with transient disruptions of epithelial junctions [9].

Regardless of the modality of epithelium airway breach, Pseudomonas aeruginosa produces virulence factors to trigger airway inflammation and damage. Of these virulence factors, type 3 secretion systems, including ExoS, ExoT, and ExoU, induce cellular death, enabling further access of bacteria to the underlying epithelial basement membrane and exposure to the vasculature [7]. Exo U in particular possesses phospholipase A2 activity that causes rapid plasma membrane disruption and necrotic cell death that aligns in the pathological features seen in necrotizing pneumonia. Recent studies have demonstrated that ExoU-positive genotype is an independent predictor of early mortality in Pseudomonas bacteremia [20]. Simultaneously, host immune responses further amplify lung injury through the activation of pro-inflammatory cytokines, including TNF-α, IL-1β, and IL-8, which ultimately contribute to collateral damage of the respiratory epithelium [7].

Lastly, Pseudomonas aeruginosa laterally propagates through a paracellular route via pili and flagella to gain further access to the other parts of the basal portions of the respiratory epithelium, thus disseminating through much of the pulmonary tissue [7].

Typical clinical presentations

The clinical manifestations of necrotizing pneumonia are usually similar, regardless of the microbial etiology.

Necrotizing pneumonia develops acutely over several days and manifests with severe sepsis, high fevers, acute hypoxic respiratory failure, hemoptysis, and other constitutional symptoms [1]. Seo et al. demonstrate in their 2017 Korean study on the incidence and clinical features of necrotizing pneumonia that the typical patient demographics for those most likely to develop necrotizing pneumonia are those with heavy alcohol use, gastrectomies, and smokers [3]. Similarly, Li et al. further amplified the typical patient demographics by correlating necrotizing pneumonia with smoking, underlying pulmonary diseases, or immunocompromised statuses such as HIV [10].

Complications of necrotizing pneumonia are common and entail both local and systemic sequelae. Common complications entail parapneumonic effusions, empyema, pneumothorax, and bronchopleural fistulas, often requiring procedural interventions with a chest tube drainage or surgical interventions [11]. Bacterial and metastatic infections (e.g., distant abscesses) are also possible, especially when the organism is highly virulent [12].

Diagnosis

The diagnosis of necrotizing pneumonia primarily rests on pulmonary imaging through a CT with contrast, which often depicts multi-lobar wall cavitation lesions and areas of necrosis with right middle and lower lobes most commonly affected [11]. Additionally, patients may also have elevated erythrocyte sedimentation rates (ESR), C-reactive proteins (CRP), and leukocytosis or leukopenia [3]. Necrotizing pneumonia should further be suspected in patients with severe pneumonia that do not respond appropriately to antibiotic therapy and if they have worsening leukocytosis/leukopenia, persistent fevers, or markers of inflammation.

Culture of the respiratory tract via sputum, endotracheal aspirate, or bronchoalveolar lavage is necessary for identifying the causative pathogen and providing targeted antimicrobial therapy [1].

Medical treatment and surgical treatment

Necrotizing pneumonia management primarily involves medical therapy, with surgical interventions reserved for select cases.

Medically, antibiotics are the cornerstone of treatment for necrotizing pneumonia. Without the known causative microbe, empirical antimicrobial therapy is necessary and depends on whether the pneumonia is community- or hospital-acquired [2]. In cases where community-acquired necrotizing pneumonia is suspected, American Thoracic Society (ATS) and Infectious Disease Society of America (IDSA) guidelines recommend a regimen of ampicillin-sulbactam and a macrolide. Methicillin-resistant Staphylococcus aureus (MRSA) coverage with linezolid or vancomycin is reserved for patients with risk factors. Moreover, in hospital-acquired necrotizing pneumonias, coverage with anti-pseudomonal antimicrobials is necessary alongside coverage for MRSA [13]. Expert opinions have generally been expressed on extended antibiotic courses, ranging from two to four weeks.

Aside from antibiotic therapy, other medical therapies include the use of corticosteroids to blunt the inflammatory response in pneumonia [2]. While research is limited, the CAPE COD trial in 2023 was able to show that among patients with severe community-acquired pneumonia treated in the medical intensive care unit (MICU), patients treated with hydrocortisone had a lower risk of death than those without therapy, indicating some potential benefits of steroids to an extrapolated population of necrotizing pneumonia patients [14].

Surgery indications vary between guidelines. The most widely accepted indication for surgery entails failure of medical therapy with ongoing clinical deterioration, the development of life-threatening hemoptysis with a clear surgical intervention pathway, extensive gangrene, or significant complications from necrotizing pneumonia such as an empyema [2, 15]. Surgical options include lobectomy, cavitary debridement, and video-assisted thoracoscopic surgery/decortication. Mortality risks are extremely high with surgical interventions; thus, preference entails exhausting other procedural interventions through bronchoscopy use, chest tube drainage, and embolization therapy [16].

Risks of adalimumab therapy

Center to this case report is the use of adalimumab therapy for psoriasis and its risks for infectious complications. Tumor necrosis factor (TNF) and interleukin-1 (IL-1) have largely been shown to be critical pathogenic markers in inflammatory conditions, including psoriasis. Long-term use of anti-TNFα agents, such as adalimumab, has been associated with an increased risk of infections, malignancies, tuberculosis, and soft-tissue infections. While the dangers of tuberculosis and other granulomatous infections have been reported in post-marketing surveillance, there is no consensus on the risks of other infections associated with anti-TNFα agents [17]. Concomitant immunosuppressive therapy, underlying comorbidities, and patient age may influence the magnitude of risk for infections. Patients are thus frequently monitored for risks and evidence of infections, especially tuberculosis, while on adalimumab therapy.

The mechanism of TNF is crucial to the response of bacterial diseases in infected patients. TNF assists in the recruitment, activation, and efficiency of immune cells as well as the development of granulomas. TNF also plays a critical role in stimulation of cytokine production, tissue repair, and cellular growth. The end result of TNF functions lead to several biological effects including fever, tissue inflammation, and the production of acute phase proteins promoting cellular defense. Anti-TNFα agents such as adalimumab block interactions of TNF with its associated cell-surface receptors thereby blunting the infectious response mechanisms produced by the host. A risk of bacterial infections such as Pseudomonas aeruginosa are hypothesized to be increased due to these effects [21].

Case presentation

A 70-year-old male with a past medical history of chronic obstructive pulmonary disease (utilizes oxygen as needed at home) (COPD), chronic hepatitis C and alcohol induced liver cirrhosis (has been sober for past 15 years), chronic thrombocytopenia, stage III chronic kidney disease, esophageal varices without bleeding, and plaque psoriasis on adalimumab 40 mg every two weeks for the past three years (has historically had negative QuantiFERON TB Gold tests) presented to a level-one trauma center emergency department with complaints of shortness of breath, chest pain, and one day of hemoptysis. The patient reported that these symptoms developed spontaneously without any known exposure to sick contacts, environmental triggers, or other causes. The patient had reported that his chest pain was described as central and worsened with inspiration. He described the cough as productive with a yellow phlegm that transitioned to hemoptysis one day before admission. He attempted to increase his oxygen to little clinical relief of his symptoms.

Upon arrival at the emergency department, the patient’s vitals were: blood pressure of 79/50 mmHg, heart rate of 88 beats/min, respiratory rate of 22 breaths/min, and temperature of 36.8 °C. Initial lab workup was notable for lactic acid of 3.2 mmol/L (normal: 0.5–2.2 mmol/L), creatinine of 1.91 mg/dL (patient’s baseline creatinine is approximately 1.34 mg/dL) (normal: 0.70–1.30 mg/dL), white blood cell count of 1.45 × 10^3/uL (normal: 4.00–10.60 × 10^3/uL) with a neutrophil predominance of about 90.5%, hemoglobin of 8.7 g/dL (normal: 13.0–17.0 g/dL), platelets of 34 × 10^3/uL (normal: 150–400 × 10^3/uL), and an ABG demonstrating a pH of 7.32 (normal: 7.35–7.45), pCO2 of 35 mmHg (normal: 35–45mmHg), and pO2 of 142 mmHg (normal: 83–108 mmHg) on high flow nasal cannula oxygen with FiO2 of 100%. The remainder of his chemistry panel and high-sensitivity troponins were largely unremarkable. The patient had a chest x-ray completed, demonstrating an 8 cm cavitary opacity in the left apex (Fig. 1: Admitting Chest X-Ray). A CT angiogram (CTA) of the chest was completed to rule out a pulmonary emboli. Results of the CTA chest demonstrated no pulmonary emboli, but a significant left upper lobe airspace opacity with central cavitation and diffuse peripheral non-specific reticulonodular opacities (Fig. 2: Admitting CTA of Chest).

Fig. 1.

Admitting Chest X-Ray

Fig. 2.

Admitting CTA of Chest

After the initial workup, the patient was admitted to the MICU and started on intravenous ceftriaxone and azithromycin, pressor support after central line placement was obtained, and fluid resuscitation. Further diagnostic workup entailed testing for Aspergillus galactomannan antigen, 1–3-beta-d-glucan, urine histoplasma antigen, Legionella urine antigen, and Streptococcus pneumoniae urine antigen, which were ultimately unremarkable.

On day two of hospitalization, the initial blood cultures and sputum cultures rapidly grew Pseudomonas aeruginosa, for which antibiotics were immediately transitioned to intravenous cefepime. The patient eventually worsened clinically and ultimately required rapid sequence intubation and bronchoscopy, revealing old crusty/bloody secretions in the left upper apical-posterior segment of the left upper lobe. Acid-fast bacilli cultures obtained in bronchoscopy were negative, but respiratory cultures on the left lung bronchial washing confirmed more than 10,000 colony-forming units/mL of Pseudomonas aeruginosa. Due to worsening pressor requirements, clinical condition, metabolic parameters, and the pending sensitivities of the Pseudomonas infection, the patient was broadened to ceftolozane-tazobactam and initiated on continuous venovenous hemodialysis (CVVHD). A repeat CT chest was obtained, demonstrating significant interval worsening in ground-glass opacities in the right greater than left, proximal cavitation within the right upper lobe, and redemonstrated large solid and cavitary lesions of the lung with an increase in size (Fig. 3: Repeat CT Chest on Day 2 of Hospitalization).

Fig. 3.

Repeat CT Chest on Day 2 of Hospitalization

On day three of hospitalization, the patient’s septic shock continued to worsen, requiring triple pressors. The sensitivities for Pseudomonas revealed pan-sensitivities to all anti-pseudomonal agents, and antibiotics were changed to intravenous meropenem (Table 1: Pseudomonas Aeruginosa MIC Patterns). Sensitvity patterns were the same for both the blood and sputum strain of Pseduomonas. A repeat bronchoscopy was performed, demonstrating significant airway inflammation in the endobronchial branches, which was diffusely present. A left-sided chest tube was placed given pulmonary findings concerning a left pleural effusion; however, the family opted to transition goals of care to comfort care only, and the patient passed away on day four of hospitalization (Fig. 4: Timeline Overview of Patient’s Course).

Table 1.

Pseudomonas aeruginosa MIC patterns

Antibiotic	Pseudomonas Aeruginosa MIC
Cefepime	2 ug/ml
Ciprofloxacin	</= 0.25 ug/ml
Levofloxacin	</= 0.5 ug/ml
Meropenem	</= 0.5 ug/ml
Piperacillin/Tazobactam	8/4 ug/ml
Tobramycin	</= 2 ug/ml

Fig. 4.

Timeline Overview of Patients's Course

Discussion and conclusion

The patient, with a multitude of stable medical comorbidities on chronic adalimumab therapy for plaque psoriasis, presented with acute and rapidly deteriorating infectious pulmonary symptoms. The unifying diagnosis to explain all of the patient’s symptoms, clinical decline, and ultimate death is necrotizing pneumonia and bacteremia induced solely by Pseudomonas aeruginosa. This case exemplifies several essential discussion points.

Reflection of the case

With respect to the patient’s disease progression, the patient undoubtedly contracted Pseudomonas aeruginosa in the community through inhalation of the microbe. He had no healthcare exposure to deem this a hospital-acquired pneumonia. Given that he initially had only chest pain, cough, and yellow productive phlegm, he likely had symptoms purely attributed to a community-acquired pneumonia. Within 24–36 h and before he visited the hospital, it is clear that this community-acquired pneumonia transitioned to a necrotizing pneumonia hallmarked by the manifestation of hemoptysis. Moreover, during that time, he likely became bacteremic through the vascular invasion of Pseudomonas aeruginosa in his lungs [7], as evidenced by profound leukopenia on admission, with the short time to positivity of his blood cultures. By the time he had been admitted to the MICU, he likely already had advanced necrotizing disease that was far from curative.

The differential diagnosis and clinical workup allowed us to eliminate common pathologies and diagnose this rare phenomenon quickly. In the workup of this patient with infectious pulmonary symptoms, several differential diagnoses were considered and investigated. Lung malignancy was considered, given the patient’s hemoptysis, COPD, and cavitary radiographic imaging. We were able to quickly rule this out, given further pulmonary delineations through a dedicated chest CT, blood and respiratory cultures proving Pseudomonas aeruginosa, and the acuity of his condition. Given the fact that he was on chronic adalimumab therapy, had hemoptysis, and cavitary pulmonary imaging, tuberculosis was considered in our differentials. Due to our initial suspicion of tuberculosis, the patient was placed in airborne precautions until acid-fast bacilli cultures obtained from the bronchoscopy were negative, thus ruling out tuberculosis as the likely disease. Our suspicion rested primarily on a community-acquired pneumonia inducing septic shock - specifically, Streptococcus pneumoniae and atypical organisms were mainly suspected. Once Pseudomonas aeruginosa was confirmed through blood and respiratory cultures, the likelihood of these organisms contributing to his illness diminished.

Retrospectively analyzing this case, numerous strengths were evident in the management of this patient among the medical teams. First, the time to admit, stabilize, and treat the patient was swift. The patient was quickly triaged in the emergency department, and the MICU team was consulted within minutes after the initial lab results and images were obtained. The admission time to the MICU after the initial consultation occurred within minutes, and the patient was appropriately recognized as having a pulmonary and infectious process, as suggested by imaging and clinical impressions. Furthermore, he underwent prompt procedural interventions. His central line was placed immediately upon admission, followed by initiation of pressors and 30mL/kg fluid resuscitation. Intubation and bronchoscopy were performed immediately once he showed intolerance to non-invasive ventilation, trialed for several hours in the MICU. A chest tube was placed as soon as complications of an empyema from his necrotizing pneumonia were detected. Second, the infectious disease team appropriately adjusted antibiotics to match the pace at which diagnostic information became available, as well as the patient’s clinical deterioration. Once both blood and sputum cultures were positive for Pseudomonas aeruginosa, antibiotics were appropriately adjusted to cefepime on day 2 of admission. Given his worsening metabolic parameters and respiratory status, antibiotics were broadened, in abundance of precaution, to ceftolozane-tazobactam to target a potential multidrug-resistant Pseudomonas aeruginosa. By day 3, sensitivities were finalized, yielding a pan-susceptible Pseudomonas aeruginosa, for which antibiotics were changed to meropenem.

One of the identifiable flaws within the patient’s treatment course was the choice of initial antibiotics utilized. Upon admission, the patient was empirically started on treatment for community-acquired pneumonia with ceftriaxone and azithromycin – antibiotics that have no targeted activity against Pseudomonas aeruginosa. The patient had no strong risk factors associated with pseudomonal pneumonia including recent hospitalizations, known Pseudomonas colonization, or receipt of antibiotics in the past three months as outlined by ATS guidelines [13]. However, the patient had minor risk factors for warranting pseudomonal coverage with a history of COPD and immunosuppression [13]. The patient received targeted antibiotic treatment with cefepime only after 12–18 h of being in the hospital. Hindsight, these conditions would have been some indications to empirically broaden antibiotics for pseudomonal coverage. Given the manifestations of septic shock, the necrotizing features that were present before admission, and the evidence of overwhelming infection as noted by his leukopenia on admission, clear end-organ damage had already ensued, and twelve hours of earlier targeted antimicrobial therapy alone would not have likely changed outcomes.

Supplemental therapy for necrotizing pneumonia was appropriately considered but declined. Of the available options, a cardiothoracic surgery consultation for surgical interventions (e.g., lobectomy, decortication, etc.) was entertained; however, it was dismissed given the patient’s extremely poor surgical candidacy, being on three pressors, acutely decompensating, and high mortality likelihood in the operating room [16]. Empiric steroids were also entertained but held off due to the initial diagnostic considerations of tuberculosis [14]. By the time tuberculosis was effectively ruled out, the patient had a significant clinical decline, and steroids were not anticipated to be significantly helpful.

Impact of the case to medical literature

This case has several important implications for expanding the current medical literature.

First, there is a dearth of reported necrotizing pneumonia induced by Pseudomonas aeruginosa. What is more unique to this case is that it is one of the few cases reporting a community-acquired Pseudomonas aeruginosa necrotizing pneumonia with no known exposure [6]. Most other reported Pseudomonas aeruginosa necrotizing pneumonia cases were either hospital-acquired or, of the community-acquired cases, had an identifiable exposure to aerosols of contaminated water [6]. This patient had no recent hospital encounters to explain Pseudomonas aeruginosa susceptibility nor were any specific aerosolized exposures noted.

Second, this case clinically reinforces the limited literature on the pathogenesis of Pseudomonas aeruginosa necrotizing pneumonia. One possible explanation for this patient contracting Pseudomonas aeruginosa in the community was his predisposed COPD-induced airway injury. Pathogenically, it is hypothesized that Pseudomonas aeruginosa invades the basolateral aspects of respiratory epithelial cells, subsequently secretes a multitude of virulence factors, and finally disseminates paracellularly, infiltrating other pulmonary and vascular tissue [7]. The patient’s clinical progression of pneumonia symptoms (with yellow phlegm production) followed by necrotizing pneumonia symptoms (hemoptysis) followed by evidence of bacteremia matches these pathogenic steps [7]. Moreover, although molecular diagnostic testing of the Pseudomonas strain was not completed, determination of high risk virulent factors such as type III secretion system and its effector cytokines may have been able to provide some prognostic information from a pathogenic perspective.

Third, this case reinforces evidence that other risk factors exist for Pseudomonas aeruginosa pneumonia outside of well-described associations of recent hospitalizations and antibiotic use in the past three months. Currently, the most well defined indication for pseudomonal coverage in community acquired pneumonia cases stems from these risk associations; however, clinicians should recognize that other lesser correlated risk factors for Pseduomonas aeruginosa pneumonia exist including COPD, immunocompromised conditions, and the local microbial epidemiology data [13].

Lastly, our patient was uniquely on adalimumab therapy. Despite adalimumab’s known immunosuppressive effects, there are unclear associations between adalimumab and Pseudomonas aeruginosa necrotizing pneumonia [17]. Adalimumab is primarily linked to an increased risk of other opportunistic infections such as tuberculosis and fungal diseases [17]. Our review has not illustrated any cases of Pseudomonas aeruginosa necrotizing pneumonia in patients on adalimumab therapy. While adalimumab-induced pulmonary disease can occur, the literature describes non-infectious pulmonary toxicities, including interstitial pneumonias, granulomatous pneumonitis, and chronic eosinophilic pneumonia [18, 19]. Extensive infectious workups in patients with adalimumab-induced pulmonary disease have not demonstrated isolations of Pseudomonas aeruginosa [18, 19]. This patient was predisposed from the immunosuppressive effects of adalimumab, but it should be noted he had a multitude of other comorbidities, including COPD with airway injury and chronic kidney disease, to explain how he was susceptible to Pseudomonas aeruginosa necrotizing pneumonia [7]. Nevertheless, given the limited literature on this topic, we are reporting this observation, but by no means concluding an association that adalimumab directly causes necrotizing pneumonia induced by Pseudomonas aeruginosa. Empirical antibiotic treatment in these patients thus does not differ from non-adalimumab therapy cases of necrotizing pneumonia. Clinicians though should have reserved vigilance when treating patients presenting with respiratory distress on biological therapy especially in face of co-existing structural lung diseases.

Abbreviations

HIV

Human Immunodeficiency Virus

HTLV-1

Human T-lymphotropic Virus Type 1

MICU

Medical Intensive Care Unit

ESR

Erythrocyte Sedimentation Rates

CRP

C-Reactive Proteins

CTA

CT Angiogram

ATS

American Thoracic Society

IDSA

Infectious Disease Society of America

MRSA

Methicillin-resistant Staphylococcus aureus

PVL

Panton-Valentine Leucocidin

IVIG

Intravenous Immunoglobulin

TNF

Tumor Necrosis Factor

IL-1

Interleukin-1

COPD

Chronic Obstructive Pulmonary Disease

CVVHD

Continuous Venovenous Hemodialysis

Authors’ contributions

Conceptualization, methodology and formal analysis: B.R., B.B., B.S., J.K. Data acquisition: B.R., B.B., B.S., J.K. Writing – original draft preparation: B.R., H.E., C.H., Writing – review and editing: B.R., H.E., C.H., F.S. Supervision: H.E., C.H. F.S. Project administration: B.R., H.E., C.H., F.S. All authors have read and agree to the published version of the manuscript.

Funding

There is no source of funding in submission of this report.

Data availability

Data analyzed during the study is available from the authors on request. All data generated or analyzed during this study are included in this published article. Data can be requested by contacting author, Branavan Ragunanthan M.D. (branavan.ragunanthan@utoledo.edu).

Declarations

Ethics approval and consent to participate

Submission of case report aligned with University of Toledo IRB protocols. Next of kin provided written consent for publication of patient’s case.

Consent for publication

Next of kin provided written consent for publication of patient’s case. Written consent available upon request.

Competing interests

The authors declare no competing interests.