Unveiling the Unexpected—Role of Unique Pathogens in Necrotizing Cavitary Pneumonia of Sickle Cell Disease: A Case Report

Abstract

Sickle cell disease (SCD), prevalent in African Americans, is associated with numerous complications, including infections and pulmonary manifestations. Necrotizing cavitary pneumonia, a rare but severe complication, poses significant diagnostic challenges in patients with SCD. We report a 27-year-old male with SCD and history of pulmonary infarction from pulmonary embolism who presented with bilateral wrist pain, cough, and chest pain and was found to have necrotizing cavitary pneumonia. Initial imaging revealed significant right upper lobe cavitary consolidation. Despite negative sputum cultures, blood cultures identified Staphylococcus epidermidis and Granulicatella, atypical pathogens in pneumonia cases. Pain crisis treatment and treatment with antibiotics for pneumonia displayed significant improvement in symptoms. Our case highlights the necessity of considering unusual pathogens in SCD patients presenting with pneumonia, particularly those with prior pulmonary complications. Infections remain a leading cause of morbidity and mortality in SCD, underscoring the importance of rapid diagnosis and tailored management. Vigilant monitoring of cavitary lesions and prompt recognition of atypical pathogens can mitigate risks of severe pulmonary complications and improve patient outcomes. Additional research is required to delineate the epidemiology of rare infections in SCD and establish effective treatment protocols.

Introduction

Sickle cell disease (SCD) comprises a spectrum of hemoglobinopathies caused by autosomal-recessive mutations in the gene encoding the beta subunit of hemoglobin (Hb) resulting in the replacement of negatively charged glutamine with neutral valine at the sixth codon of beta globin chain. SCD includes sickle cell anemia (SCA), hemoglobin SC (HbS) disease, hemoglobin sickle-beta-thalassemia (beta-thalassemia positive or beta-thalassemia negative), and sickle cell trait, in which SCA is the most severe form of the disease leading to chronic hemolytic anemia requiring blood transfusions, pain crises, and organ damage. ¹ Historically, SCD is more prevalent in sub-Saharan Africa, however, recent data shows that approximately 100 000 Americans have SCD. ² CDC estimates that 1 in 13 babies born to African-American parents have sickle cell trait, and 1 in 365 African-Americans have SCD. ¹

The pathophysiology of SCD falls under 4 major pathways—hemolysis-mediated endothelial dysfunction, vaso-occlusion, HbS polymerization, and sterile inflammation. The mutated hemoglobin (HbS) molecules polymerize to form bundles, which result in sickling of erythrocytes leading to vaso-occlusion, promoting ischemia-reperfusion injury. Hemoglobin polymer bundles also promote hemolysis, releasing cell-free Hb to the bloodstream. Oxygenated hemoglobin promotes endothelial dysfunction by decreasing endothelial nitric oxide and producing free radicals and methemoglobin. Cell-free heme from hemolysis and ischemia reperfusion injury from vaso-occlusion contributes to sterile inflammation through the activation of the inflammasome pathway in inflammatory and vascular cells to produce IL-1β. Lastly, a feedback loop promotes adhesions of platelets, neutrophils, and endothelial cells caused by sterile inflammation which further promotes vaso-occlusion through. ³

The clinical manifestations of SCA include direct and indirect consequences of these pathophysiologic mechanisms. The most common acute complications of SCA are acute chest syndrome, sequestration crisis, acute stroke, aplastic crisis, acute intrahepatic cholestasis, infections, priapism, and ocular complications (hyphema, orbital infarction orbital compression syndrome, central retinal artery occlusion). Chronic complications comprise of iron overload, avascular necrosis of joints, leg ulcers, pulmonary artery hypertension, renal dysfunction (hyposthenuria, renal papillary necrosis, asymptomatic proteinuria), and proliferative sickle retinopathy. ¹

Infections remain the leading cause of mortality in SCA. Splenic dysfunction, complement activation defects, micronutrient deficiencies (zinc), genetic polymorphism, and mechanical factors (bone marrow expansion with poor circulation, iatrogenic transmission from transfusions and catheters) are some proposed mechanisms of the same. ⁴ As the prevalence of SCD follows an upward trajectory, the occurrence of atypical presentations and unique pathogens becomes common. Here, we describe the case of a young male with SCD with a history of acute chest syndrome and pulmonary embolism with infarction who got infected with an unusual pathogen Granulicatella leading to necrotizing cavitary pneumonia. Granulicatella, or “nutritionally variant streptococci” previously included under Abiotrophia, is a common commensal of oral flora, often involved in invasive infections like infective endocarditis. ⁵

Case Description

We report the case of a 27-year-old male with past medical history significant for SCA (HbSS), right femoral deep vein thrombosis (s/p thrombectomy), and pulmonary embolism (with right lung infarction) 3 years ago presented to the Emergency Department with 2 days of bilateral wrist pain, productive cough with minimal sputum production and pain in his chest. He also had a history of multiple admissions for acute chest syndrome and pain crisis in the past 2 years requiring exchange transfusions. A review of systems was otherwise negative for fever, shortness of breath, palpitation, dizziness, abdominal pain, skin ulcers, or leg swelling.

Vitals on admission showed a temperature of 99.1, heart rate of 76, blood pressure of 110/64, respiratory rate of 20, and saturation of 99% on room air. Physical examination showed tenderness to palpation over bilateral wrists with a restricted range of motion secondary to pain. Chest examination revealed clear breath sounds with no rhonchi, crackles, or wheezing. Cardiovascular, abdominal, and neurologic exams were unremarkable. Relevant admission labs are listed in Table 1.

Table 1.

Relevant Admission Labs.

Relevant admission labs (Admission day 1)
Hemoglobin	11.3 (Low)
Hematocrit	33 (Low)
RBC	3.88 (Low)
Mean Corpuscular Volume	85 (Normal)
Mean Corpuscular Hemoglobin	29 (Normal)
Mean Corpuscular Hemoglobin Concentration	34.4 (Normal)
Red cell Distribution Width	123.5 (High)
White blood cells	8.6 (Normal)
Platelets	294 (Normal)
Lactate dehydrogenase	428 (High)
Reticulocyte count	7.7 (high)
Hemoglobin electrophoresis	89.2% HbS
Sickle cell solubility test	Positive
Blood culture (Admission day 1)	Coagulase negative staphylococcus, Granulicatella 2/4 bottles
Blood culture (Admission day 2)	Granulicatella 2/4 bottles
Blood culture (Admission day 3)	No growth
Urinalysis	Normal
Total bilirubin	4.0 (High)
Direct bilirubin	0.7 (High)
Aspartate Aminotransferase	33 (Normal)
Alanine Aminotransferase	6 (Normal)
Alkaline Phosphatase	114 (Normal)
Erythrocyte Sedimentation Rate	3 (Normal)
C Reactive Protein	3.65 (Normal)
Lactic acid	1.0 (Normal)
Sodium	140 (Normal)
Potassium	3.9 (Normal)
Magnesium	1.6 (Normal)
Phosphorous	3.1 (Normal)
Calcium	9.4 (Normal)

Investigations: Chest X-ray on admission showed right upper lobe scarring and cavities. A CT scan of the chest was performed, which showed a large consolidation of the right upper lobe with a sizable cavity component, measuring upward of 5.6 cm exhibiting thick and thin bordered with few septations at the site of infarction (Figures 1-3).

Figure 1.

CT findings of cavitary pneumonia.

Figure 2.

CT findings of cavitary pneumonia.

Figure 3.

X-ray findings of cavitary pneumonia.

Sputum culture was negative for bacteria and fungi with negative Acid-fast bacilli culture. However, blood cultures grew Granulicatella and coagulase-negative staphylococcus. Repeat blood cultures also grew Granulicatella. Patient was admitted for management of sickle cell pain crisis and necrotizing cavitary pneumonia and was treated with intravenous antibiotics, intravenous hydration, opioids, and incentive spirometry with improvement of symptoms. Broad spectrum antibiotics (vancomycin and cefepime) were started with significant clinical improvement, later deescalated to cefazolin, based on culture results that was continued for a total of 14 days. Patient was advised to follow with a pulmonologist to monitor the resolution of cavitary lesions and with a hematologist for possible initiation of disease-modifying therapy like hydroxyurea to prevent frequent crises. Follow-up CT of the chest performed a month later redemonstrated the cavitary lesion with decreased surrounding consolidation and ground glass attenuation.

Discussion

SCD patients are prone to infections with a multitude of pathogens:

• Encapsulated bacteria: Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae causing respiratory infections and fulminant sepsis. Functional hypo or asplenism from SCD results in defective synthesis of immunoglobulins and immunostimulatory peptides like tuftsin and properdin impairing complement activation. Infection with encapsulated bacteria occurs due to defective opsonization and lack of IgM memory B cells to mount effective immune response in subsequent encounters. ⁶

• Eschericia coli, Mycoplasma pneumoniae, Chlamydophila pneumoniae, and Anaerobes: E. coli urinary tract infection, respiratory infections with Mycoplasma and Chlamydophila, cholecystitis and dental infections with anaerobes occurs in SCD due to defects in alternate complement pathway and reduced neutrophil mediated phagocytosis. ⁷

• Salmonella and Staphylococcus aureus can cause osteomyelitis in the necrotic bone, which can occur due to expansion of bone marrow coupled with poor circulation from vaso-occlusion rendering bone vulnerable to infarction. ⁸

• Edwardsiella tarda infections are increasing in SCD, possibly due to increased gut permeability and biliary sludging. ⁹

• Human immunodeficiency virus, Hepatitis B and C virus, Cytomegalovirus, and Parvovirus B19 infections occur in SCD more than the general population, attributable to chronic transfusions and related transmission of infections. ¹⁰ Increased red cell turnover also predisposes to Parvovirus B19 infection. ⁴

• Yersinia enterocolitica. Due to iron overload from repeated transfusions. ⁴

S. pneumoniae, H. influenzae, and M. pneumoniae remain the most prevalent cause of respiratory infections in SCD. Infections in acute chest syndrome have been identified in association with many pathogens, with Chlamydia pneumoniae and M. pneumoniae being the most common. ¹¹

Necrotizing pneumonia is a severe form of bacterial pneumonia which results in pneumonic consolidation with multiple necrotic foci in the parenchyma of the lung. ¹² It results from an inflammatory response triggered by toxins produced by the invading pathogen, or by associated vasculitis or thrombosis. S. aureus and S. pneumoniae cause most cases of necrotizing pneumonia in otherwise healthy patients. ¹² In S. aureus, the cytotoxin Panton-Valentine Leukocidin and alpha-hemolysin lead to tissue destruction, whereas in S. pneumoniae, the inflammatory response to capsular polysaccharide and its ability to resist phagocytosis aids in the formation of necrosis. ¹³ Klebsiella pneumoniae and Streptococcus viridans were identified as the causative agents in a subset of patients, especially in immunocompromised and alcoholic individuals.^14,15 Hyperviscosity and K1/K2 capsular serotype act as virulence factors in Klebsiella and M protein plays this role in S. viridans. Rare reports of necrotizing pneumonia from Burkholderia cepacia, ¹⁶ Pseudomonas aeruginosa (due to thrombotic endarteritis), ¹⁷ Clostridium species, ¹⁸ M. pneumoniae, ¹⁹ and E. coli, ²⁰ were also reported in literature.

Studies of coagulase negative staphylococcus causing necrotizing pneumonia are exceedingly rare and to our knowledge, there are about 2 cases reported so far. Carpio-Orantes reported a case of Staphylococcus epidermidis causing cavitary pneumonia in an immunocompetent host ²¹ and a case of S. epidermidis necrotizing pneumonia and pneumatocele in a neonate were described in literature. ²² Granulicella, the other pathogen identified in our case is a fastidious bacteria known as “nutritionally variant streptococci” which causes blood stream infections, endocarditis, and prosthetic material infection. Granulicella causing lung infections has never been reported before. ⁵ Whether this contributed to the cavitary pneumonia in our patient remains a curious diagnostic challenge.

Conclusion

SCD significantly contributes to morbidity and mortality in the United States, with infections being a major cause of death. Acute chest syndrome and lung infections complicate the disease, necessitating empirical treatment targeting common pathogens while awaiting culture results. Identifying rare pathogens in cavitary pneumonia is crucial for effective management, especially in individuals with a history of pulmonary infarction, which increases infection risk. Vigilant monitoring and tailored strategies are essential to improve outcomes and minimize the risk of pulmonary complications in this vulnerable population.